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Original Articles

A critical review of the postulated role of the non-essential amino acid, β-N-methylamino-L-alanine, in neurodegenerative disease in humans

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References

  • Abdel-Salam, O. M. E. 2014. The paths to neurodegeneration in genetic Parkinson’s disease. CNS Neurological Disorders Drug Targets 13:1485–512. doi:10.2174/1871527313666140806142955.
  • Abraham, E. P., and G. G. Newton. 1960. Chemistry and classification of antibiotics. British Medical Bulletin 16:3–10. doi:10.1093/oxfordjournals.bmb.a069788.
  • Ahlskog, J. E., S. C. Waring, L. T. Kurland, R. C. Petersen, T. P. Moyer, W. S. Harmsen, D. M. Maraganore, P. C. O’Brien, C. Esteban-Santillan, and V. Bush. 1995. Guamanian neurodegenerative disease: Investigation of the calcium metabolism/heavy metal hypothesis. Neurology 45:1340–44. doi:10.1212/WNL.45.7.1340.
  • Al-Sammak, M. A., K. D. Hoagland, D. Cassada, and D. D. Snow. 2014. Co-occurrence of the cyanotoxins BMAA, DABA and anatoxin-a in Nebraska reservoirs, fish, and aquatic plants. Toxins (Basel) 6:488–508. doi:10.3390/toxins6020488.
  • Anderson, F. H., E. P. Richardson, Jr.H. Okazaki, and J. A. Brody. 1979. Neurofibrillary degeneration on Guam: Frequency in Chamorros and non Chamorros with no known neurological disease. Brain 102:65–77. doi:10.1093/brain/102.1.65.
  • Appenzeller, B. M., and A. M. Tsatsakis. 2012. Hair analysis for biomonitoring of environmental and occupational exposure to organic pollutants: State of the art, critical review and future needs. Toxicology Letters 210:119–40. doi:10.1016/j.toxlet.2011.10.021.
  • Araki, S., Y. Iwahashi, and Y. Kuroiwa. 1967. Epidemiological study of amyotrophic lateral sclerosis and allied disorders in the Kii Peninsula (Japan). Journal of the Neurological Sciences 4:279–87. doi:10.1016/0022-510X(67)90106-2.
  • Arnold, A., D. C. Edgren, and V. S. Palladino. 1953. Amyotrophic lateral sclerosis: Fifty cases observed on Guam. The Journal of Nervous and Mental Disease 117:135–39. doi:10.1097/00005053-195302000-00005.
  • Ashraf, G. M., N. H. Greig, T. A. Khan, I. Hassan, S. Tabrez, S. Shakil, et al. 2014. Protein misfolding and aggregation in Alzheimer’s disease and type 2 diabetes mellitus. CNS & Neurological Disorders Drug Targets 13:1280–93. doi:10.2174/1871527313666140917095514.
  • Bailey-Wilson, J. E., C. C. Plato, R. C. Elston, and R. M. Garruto. 1993. Potential role of an additive genetic component in the cause of amyotrophic lateral sclerosis and Parkinsonism-Dementia in the western Pacific. American Journal of Medical Genetics 45:68–76. doi:10.1002/(ISSN)1096-8628.
  • Banack, S. A. 1998. Diet selection and resource use by flying foxes (Genus Pteropus). Ecology 79:1949–67. doi:10.1890/0012-9658(1998)079[1949:DSARUB]2.0.CO;2.
  • Banack, S. A., T. Caller, P. Henegan, J. Haney, A. Murby, J. S. Metcalf, J. Powell, P. A. Cox, and E. Stommel. 2015. Detection of cyanotoxins, beta-N-methylamino-L-alanine and microcystins, from a lake surrounded by cases of amyotrophic lateral sclerosis. Toxins 7:322–36. doi:10.3390/toxins7020322.
  • Banack, S. A., and P. A. Cox. 2003a. Biomagnification of cycad neurotoxins in flying foxes: Implications for ALS-PDC in Guam. Neurology 61:387–89. doi:10.1212/01.WNL.0000078320.18564.9F.
  • Banack, S. A., and P. A. Cox. 2003b. Distribution of the neurotoxic nonprotein amino acid BMAA in Cycas micronesica. Botanic Journal Linnean Social 143:165–68. doi:10.1046/j.1095-8339.2003.00217.x.
  • Banack, S. A., H. E. Johnson, R. Cheng, and P. A. Cox. 2007. Production of the neurotoxin BMAA by a marine cyanobacterium. Marine Drugs 5:180–96. doi:10.3390/md504180.
  • Banack, S. A., J. S. Metcalf, W. G. Bradley, and P. A. Cox. 2014. Detection of cyanobacterial neurotoxin beta-N-methylamino-L-alanine within shellfish in the diet of an ALS patient in Florida. Toxicon 90:167–73. doi:10.1016/j.toxicon.2014.07.018.
  • Banack, S. A., and S. J. Murch. 2009. Multiple neurotoxic items in the Chamorro diet link BMAA with ALS/PDC. Amyotrophic Lateral Sclerosis 10 (Suppl 2):34–40. doi:10.3109/17482960903278451.
  • Banack, S. A., S. J. Murch, and P. A. Cox. 2006. Neurotoxic flying foxes as dietary items for the Chamorro people, Marianas Islands. Journal of Ethnopharmacology 106:97–104. doi:10.1016/j.jep.2005.12.032.
  • Banos, G., P. M. Daniel, and O. E. Pratt. 1978. The effect of age upon the entry of some amino acids into the brain, and their incorporation into cerebral protein. Developmental Medicine and Child Neurology 20:335–46. doi:10.1111/j.1469-8749.1978.tb15223.x.
  • Baptista, M. S., R. G. Vasconcelos, P. C. Ferreira, C. M. Almeida, and V. M. Vasconcelos. 2015. Assessment of the non-protein amino acid BMAA in Mediterranean mussel Mytilus galloprovincialis after feeding with estuarine cyanobacteria. Environmental Science and Pollution Research International 22:12501–10. doi:10.1007/s11356-015-4516-5.
  • Beard, J. D., and F. Kamel. 2015. Military service, deployments, and exposures in relation to Amyotrophic lateral sclerosis etiology and survival. Epidemiologic Reviews 37:55–70. doi:10.1093/epirev/mxu001.
  • Bell, E. A., A. Vega, and P. B. Nunn 1967. A neurotoxic amino acid in seeds of Cycas circinalis. Paper presented at Fifth Cycad Conference, Miami, FL.
  • Berntzon, L., L. O. Ronnevi, B. Bergman, and J. Eriksson. 2015. Detection of BMAA in the human central nervous system (Vol 292, Pg 137, 2015). Neuroscience 300:619–619. doi:10.1016/j.neuroscience.2015.04.008.
  • Borenstein, A. R., J. A. Mortimer, E. Schofield, Y. Wu, D. P. Salmon, A. Gamst, J. Olichney, L. F. Thal, L. Silbert, J. Kaye, U. L. Craig, G. D. Schellenberg, and D. R. Galasko. 2007. Cycad exposure and risk of dementia, MCI, and PDC in the Chamorro population of Guam. Neurology 68:1764–71. doi:10.1212/01.wnl.0000262027.31623.b2.
  • Bradley, W. G., A. R. Borenstein, L. M. Nelson, G. A. Codd, B. H. Rosen, E. W. Stommel, and P. A. Cox. 2013. Is exposure to cyanobacteria an environmental risk factor for amyotrophic lateral sclerosis and other neurodegenerative diseases? Amyotrophic Lateral Sclerosis Frontotemp Degen 14:325–33. doi:10.3109/21678421.2012.750364.
  • Bradley, W. G., and D. C. Mash. 2009. Beyond Guam: The cyanobacteria/BMAA hypothesis of the cause of ALS and other neurodegenerative diseases. Amyotrophic Lateral Sclerosis 10 (Suppl. 2):7–20. doi:10.3109/17482960903286009.
  • Brand, L. E. 2009. Human exposure to cyanobacteria and BMAA. 2009. Amyotrophic Lateral Sclerosis 10 (Suppl. 2):85–95. doi:10.3109/17482960903273585.
  • Brand, L. E., J. Pablo, A. Compton, N. Hammerschlag, and D. C. Mash. 2010. Cyanobacterial blooms and the occurrence of the neurotoxin beta-N-methylamino-L-alanine (BMAA) in south Florida aquatic food webs. Harmful Algae 9:620–35. doi:10.1016/j.hal.2010.05.002.
  • Briand, J. F., C. Leboulanger, J. F. Humbert, C. Bernard, and P. Dufour. 2004. Cylindrospermopsis raciborskii (Cyanobacteria) invasion at mid-latitudes: Selection, wide physiological tolerance, or global warming? Journal of Phycology 40:231–38. doi:10.1111/j.1529-8817.2004.03118.x.
  • Brion, J. P. 1998. Neurofibrillary tangles and Alzheimer’s disease. European Neurology 40:130–40. doi:10.1159/000007969.
  • Brody, J. A., A. H. Edgar, and M. M. Gillespie. 1978. Amyotrophic lateral sclerosis. No increase among US construction workers in Guam. Journal of the American Medical Association 240:551–60. doi:10.1001/jama.1978.03290060053013.
  • Brody, J. A., A. Hirano, and R. M. Scott. 1971. Recent neuropathologic observations in Amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam. Neurology 21:528–36. doi:10.1212/WNL.21.5.528.
  • Buee-Scherrer, V., L. Buee, P. R. Hof, B. Leveugle, C. Gilles, A. J. Loerzel, et al. 1995. Neurofibrillary degeneration in Amyotrophic lateral sclerosis/Parkinsonism dementia complex of Guam. Immunochemical characterization of tau proteins. The American Journal of Pathology 146:924–32.
  • Caller, T. A., J. W. Doolin, J. F. Haney, A. J. Murby, K. G. West, H. E. Farrar, A. Ball, B. T. Harris, and E. W. Stommel. 2009. A cluster of Amyotrophic lateral sclerosis in New Hampshire: A possible role for toxic cyanobacteria blooms. Amyotrophic Lateral Sclerosis 10:101–08. doi:10.3109/17482960903278485.
  • Caller, T. A., N. C. Field, J. W. Chipman, X. Shi, B. T. Harris, and E. W. Stommel. 2012. Spatial clustering of Amyotrophic lateral sclerosis and the potential role of BMAA. Amyotrophic Lateral Sclerosis 13:25–32. doi:10.3109/17482968.2011.621436.
  • Campbell, R. J., J. C. Steele, T. A. Cox, A. J. Loerzel, M. Belli, and D. D. Belli. 1993. Pathologic findings in the retinal pigment epitheliopathy associated with the Amyotrophic lateral sclerosis/Parkinsonism dementia complex of Guam. Ophthalmology 100:37–42. doi:10.1016/S0161-6420(93)31696-9.
  • Carr, D. J., and S. G. M. Carr, ed. 1981. The botany of the first Australians. People and plants in Australia. Sydney: Academic Press.
  • Carroll, D., and J. C. Hathaway. 1963. Mineralogy of selected soils from Guam. Geological Survey Professional Paper 403-F; Department of the Interior. Washington, DC: United States Government Printing Office.
  • Cervantes Cianca, R. C., M. S. Baptista, V. R. Lopes, and V. M. Vasconcelos. 2012. The non-protein amino acid beta-N-methylamino-L-alanine in Portuguese cyanobacterial isolates. Amino Acids 42:2473–79. doi:10.1007/s00726-011-1057-1.
  • Chatziefthimiou, A. D., J. S. Metcalf, W. B. Glover, S. A. Banack, S. R. Dargham, and R. A. Richer. 2016. Cyanobacteria and cyanotoxins are present in drinking water impoundments and groundwater wells in desert environments. Toxicon 114:75–84. doi:10.1016/j.toxicon.2016.02.016.
  • Chen, X., Y. Xia, L. S. Gresham, C. A. Molgaard, R. G. Thomas, D. Galasko, W. C. Wiederholt, and T. Saitoh. 1996. ApoE and CYP2D6 polymorphism with and without Parkinsonism dementia complex in the people of Chamorro, Guam. Neurology 47:779–84. doi:10.1212/WNL.47.3.779.
  • Chiu, A. S., M. M. Gehringer, N. Braidy, G. J. Guillemin, J. H. Welch, and B. A. Neilan. 2012. Excitotoxic potential of the cyanotoxin beta-methyl-amino-L-alanine (BMAA) in primary human neurons. Toxicon 60:1159–65. doi:10.1016/j.toxicon.2012.07.169.
  • Cohen, S. A. 2012. Analytical techniques for the detection of alpha-amino-beta-methylaminopropionic acid. The Analyst 137:1991–2005. doi:10.1039/c2an16250d.
  • Combes, A., S. El Abdellaoui, J. Vial, E. Lagrange, V. Pichon, and B. Grp. 2014. Development of an analytical procedure for quantifying the underivatized neurotoxin beta-N-methylamino-L-alanine in brain tissues. Analytical and Bioanalytical Chemistry 406:4627–36. doi:10.1007/s00216-014-7872-y.
  • Contardo-Jara, V., T. Schwanemann, and S. Pflugmacher. 2014. Uptake of a cyanotoxin, beta-N-methylamino-L-alanine, by wheat (Triticum aestivum). Ecotoxicology and Environmental Safety 104:127–31. doi:10.1016/j.ecoenv.2014.01.039.
  • Cox, P. A. 2004. Indigenous horticulturists and human health: An ethnobotanical approach. Horticulture: Art Sciences Life 642:173–85.
  • Cox, P. A., S. A. Banack, and S. J. Murch. 2003. Biomagnification of cyanobacterial neurotoxins and neurodegenerative disease among the Chamorro people of Guam. Proceedings of the National Academy of Sciences of the United States of America 100:13380–83. doi:10.1073/pnas.2235808100.
  • Cox, P. A., S. A. Banack, S. J. Murch, U. Rasmussen, G. Tien, R. R. Bidigare, J. S. Metcalf, L. F. Morrison, G. A. Codd, and B. Bergman. 2005. Diverse taxa of cyanobacteria produce beta-N-methylamino-L-alanine, a neurotoxic amino acid. Proceedings of the National Academy of Sciences of the United States of America 102:5074–78. doi:10.1073/pnas.0501526102.
  • Cox, P. A., D. A. Davis, D. C. Mash, J. S. Metcalf, and S. A. Banack. 2016. Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain. Proceedings R Social B-Biological Sciences 283:20152397. doi:10.1098/rspb.2015.2397.
  • Cox, P. A., R. Richer, J. S. Metcalf, S. A. Banack, G. A. Codd, and W. G. Bradley. 2009. Cyanobacteria and BMAA exposure from desert dust: A possible link to sporadic ALS among Gulf War veterans. Amyotrophic Lateral Sclerosis 10 (Suppl 2):109–17. doi:10.3109/17482960903286066.
  • Cox, P. A., and O. W. Sacks. 2002. Cycad neurotoxins, consumption of flying foxes, and ALS-PDC disease in Guam. Neurology 58:956–59. doi:10.1212/WNL.58.6.956.
  • Cox, T. A., J. V. McDarby, L. Lavine, J. C. Steele, and D. B. Calne. 1989. A retinopathy on Guam with high prevalence in Lytico-Bodig. Ophthalmology 96:1731–35. doi:10.1016/S0161-6420(89)32656-X.
  • Cramer, F., U. Englisch, W. Freist, and H. Sternbach. 1991. Aminoacylation of tRNAs as critical step of protein biosynthesis. Biochimie 73:1027–35. doi:10.1016/0300-9084(91)90144-P.
  • Cruz-Aguado, R., D. Winkler, and C. A. Shaw. 2006. Lack of behavioral and neuropathological effects of dietary beta-methylamino-L-alanine (BMAA) in mice. Pharmacology, Biochemistry, and Behavior 84:294–99. doi:10.1016/j.pbb.2006.05.012.
  • Dastur, D. K. 1964. Cycad toxicity in monkeys: Clinical, pathological, and biochemical aspects. Federation Proceedings 23:1368–69.
  • Dawson, R., Jr.E. G. Marschall, K. C. Chan, W. J. Millard, B. Eppler, and T. A. Patterson. 1998. Neurochemical and neurobehavioral effects of neonatal administration of beta-N-methylamino-L-alanine and 3,3ʹ-iminodipropionitrile. Neurotoxicology and Teratology 20:181–92. doi:10.1016/S0892-0362(97)00078-0.
  • De Munck, E., E. Munoz-Saez, M. T. Antonio, J. Pineda, A. Herrera, B. G. Miguel, and R. M. Arahuetes. 2013a. Effect of beta-N-methylamino-L-alanine on oxidative stress of liver and kidney in rat. Environmental Toxicology and Pharmacology 35:193–99. doi:10.1016/j.etap.2012.12.004.
  • De Munck, E., E. Munoz-Saez, B. G. Miguel, M. T. Solas, A. Martinez, and R. M. Arahuetes. 2015. Morphometric and neurochemical alterations found in l-BMAA treated rats. Environmental Toxicology and Pharmacology 39:1232–45. doi:10.1016/j.etap.2015.04.022.
  • De Munck, E., E. Munoz-Saez, B. G. Miguel, M. T. Solas, I. Ojeda, A. Martinez, C. Gil, and R. M. Arahuetes. 2013b. Beta-N-methylamino-L-alanine causes neurological and pathological phenotypes mimicking amyotrophic lateral sclerosis (ALS): The first step towards an experimental model for sporadic ALS. Environmental Toxicology and Pharmacology 36:243–55. doi:10.1016/j.etap.2013.04.007.
  • Dinis-Oliveira, R. J., F. Remiao, H. Carmo, J. A. Duarte, A. S. Navarro, M. L. Bastos, and F. Carvalho. 2006. Paraquat exposure as an etiological factor of Parkinson’s disease. Neurotoxicology 27:1110–22. doi:10.1016/j.neuro.2006.05.012.
  • Dobson, C. M. 2001. The structural basis of protein folding and its links with human disease. Philosophical Transactions of the Royal Society of London 356:133–45. doi:10.1098/rstb.2000.0758.
  • Downing, S., V. Contardo-Jara, S. Pflugmacher, and T. G. Downing. 2014. The fate of the cyanobacterial toxin beta-N-methylamino-L-alanine in freshwater mussels. Ecotoxicology and Environmental Safety 101:51–58. doi:10.1016/j.ecoenv.2013.11.028.
  • Duncan, M. W., I. J. Kopin, R. M. Garruto, L. Lavine, and S. P. Markey. 1988. 2-Amino-3 (methylamino)-propionic acid in cycad-derived foods is an unlikely cause of amyotrophic lateral sclerosis/Parkinsonism. Lancet 2:631–32. doi:10.1016/S0140-6736(88)90671-X.
  • Duncan, M. W., S. P. Markey, B. G. Weick, P. G. Pearson, H. Ziffer, Y. Hu, and I. J. Kopin. 1992. 2-Amino-3-(methylamino)propanoic acid (BMAA) bioavailability in the primate. Neurobiology of Aging 13:333–37. doi:10.1016/0197-4580(92)90047-2.
  • Duncan, M. W., J. C. Steele, I. J. Kopin, and S. P. Markey. 1990. 2-Amino-3-(methylamino)-propanoic acid (BMAA) in cycad flour: An unlikely cause of amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam. Neurology 40:767–72. doi:10.1212/WNL.40.5.767.
  • Duncan, M. W., N. E. Villacreses, P. G. Pearson, L. Wyatt, S. I. Rapoport, I. J. Kopin, S. P. Markey, and Q. R. Smith. 1991. 2-amino-3-(methylamino)-propanoic acid (BMAA) pharmacokinetics and blood-brain barrier permeability in the rat. The Journal of Pharmacology and Experimental Therapeutics 258:27–35.
  • Dunlop, R. A., P. A. Cox, S. A. Banack, and K. J. Rodgers. 2013. The non-protein amino acid BMAA Is misincorporated into human proteins in place of L-serine causing protein misfolding and aggregation. PLoS One 8:e75376. doi:10.1371/journal.pone.0075376.
  • Durlach, J., P. Bac, V. Durlach, A. Durlach, M. Bara, and A. Guiet-Bara. 1997. Are age-related neurodegenerative diseases linked with various types of magnesium depletion? Magnesium Researcher 10:339–53.
  • Eldridge, R., E. Ryan, J. Rosario, and J. A. Brody. 1969. Amyotrophic lateral sclerosis and Parkinsonism dementia in a migrant population from Guam. Neurology 19:1029–37. doi:10.1212/WNL.19.11.1029.
  • Elizan, T. S., A. Hirano, B. M. Abrams, R. L. Need, C. Van Nuis, and L. T. Kurland. 1966. Amyotrophic lateral sclerosis and Parkinsonism dementia complex of Guam. Neurological Reevaluation. Archives of Neurology 14:356–68. doi:10.1001/archneur.1966.00470100012002.
  • Ellisdon, A. M., and S. P. Bottomley. 2004. The role of protein misfolding in the pathogenesis of human diseases. IUBMB Life 56:119–23. doi:10.1080/15216540410001674003.
  • Eplett, L. 2015. Fin (the end): Putting a stop to the consumption of shark fin soup. Scientific American, July 8; https://blogs.scientificamerican.com/food-matters/fin-the-end-putting-a-stop-to-the-consumption-of-shark-fin-soup/
  • Esterhuizen, M., and T. G. Downing. 2008. Beta-N-methylamino-L-alanine (BMAA) in novel South African cyanobacterial isolates. Ecotoxicology and Environmental Safety 71:309–13. doi:10.1016/j.ecoenv.2008.04.010.
  • Esterhuizen-Londt, M., and T. G. Downing. 2011. Solid phase extraction of β-N-methylamino-L-alanine (BMAA) from South African water supplies. Water SA 37:523–27.
  • Faassen, E. J. 2014. Presence of the neurotoxin BMAA in aquatic ecosystems: What do we really know? Toxins (Basel) 6:1109–38. doi:10.3390/toxins6031109.
  • Faassen, E. J., M. G. Antoniou, W. Beekman-Lukassen, L. Blahova, E. Chernova, C. Christophoridis, A. Combes, C. Edwards, J. Fastner, J. Harmsen, A. Hiskia, L. L. Ilag, T. Kaloudis, S. Lopicic, M. Lurling, H. Mazur-Marzec, J. Meriluoto, C. Porojan, Y. Viner-Mozzini, and N. Zguna. 2016. A collaborative evaluation of LC-MS/MS based methods for BMAA analysis: Soluble bound BMAA found to be an important fraction. Marine Drugs 14:45. doi:10.3390/md14030045.
  • Faassen, E. J., F. Gillissen, and M. Lurling. 2012. A comparative study on three analytical methods for the determination of the neurotoxin BMAA in cyanobacteria. PLoS One 7:e36667. doi:10.1371/journal.pone.0036667.
  • Faassen, E. J., F. Gillissen, H. A. Zweers, and M. Lurling. 2009. Determination of the neurotoxins BMAA (beta-N-methylamino-L-alanine) and DAB (alpha-,gamma-diaminobutyric acid) by LC-MSMS in Dutch urban waters with cyanobacterial blooms. Amyotrophic Lateral Sclerosis 10 (Suppl 2):79–84. doi:10.3109/17482960903272967.
  • Falconer, I. R., and A. R. Humpage. 2005. Health risk assessment of cyanobacterial (blue-green algal) toxins in drinking water. International Journal of Environmental Research and Public Health 2:43–50. doi:10.3390/ijerph2005010043.
  • Fan, H., J. Qiu, L. Fan, and A. Li. 2014. Effects of growth conditions on the production of neurotoxin 2,4-diaminobutyric acid (DAB) in Microcystis aeruginosa and its universal presence in diverse cyanobacteria isolated from freshwater in China. Environmental Science and Pollution Research International 22:5943–51. doi:10.1007/s11356-014-3766-y.
  • Field, N. C., J. S. Metcalf, T. A. Caller, S. A. Banack, P. A. Cox, and E. W. Stommel. 2013. Linking beta-methylamino-L-alanine exposure to sporadic amyotrophic lateral sclerosis in Annapolis, MD. Toxicon 70:179–83. doi:10.1016/j.toxicon.2013.04.010.
  • Fritts, T. H., and G. H. Rodda. 1998. The role of introduced species in the degradation of island ecosystems: A case history of Guam1. Annual Reviews Ecology System 29:113–40. doi:10.1146/annurev.ecolsys.29.1.113.
  • Fujita, T., Y. Okamoto, Y. Sakagami, K. Ota, and M. Ohata. 1984. Bone changes and aortic calcification in aging inhabitants of mountain versus seacoast communities in the Kii Peninsula. Journal of the American Geriatrics Society 32:124–28. doi:10.1111/j.1532-5415.1984.tb05852.x.
  • Gajdusek, D. C. 1963. Motor-neuron disease in natives of New Guinea. The New England Journal of Medicine 268:474–76. doi:10.1056/NEJM196302282680906.
  • Gajdusek, D. C., and A. M. Salazar. 1982. Amyotrophic lateral sclerosis and Parkinsonian syndromes in high incidence among the Auyu and Jakai people of West New Guinea. Neurology 32:107–26. doi:10.1212/WNL.32.2.107.
  • Galasko, D., D. Salmon, A. Gamst, J. Olichney, L. J. Thal, L. Silbert, et al. 2007. Prevalence of Dementia in Chamorros on Guam: Relationship to age, gender, education, and APOE. Neurology 68:1772–81. doi:10.1212/01.wnl.0000262028.16738.64.
  • Galasko, D., D. P. Salmon, U. K. Craig, L. J. Thal, G. Schellenberg, and W. Wiederholt. 2002. Clinical features and changing patterns of neurodegenerative disorders on Guam, 1997–2000. Neurology 58:90–97. doi:10.1212/WNL.58.1.90.
  • Garruto, R. M., R. Fukatsu, R. Yanagihara, D. C. Gajdusek, G. Hook, and C. E. Fiori. 1984a. Imaging of calcium and aluminum in neurofibrillary tangle-bearing neurons in Parkinsonism-dementia of Guam. Proceedings of the National Academy of Sciences of the United States of America 81:1875–79. doi:10.1073/pnas.81.6.1875.
  • Garruto, R. M., C. Gajdusek, and K. M. Chen. 1980. Amyotrophic lateral sclerosis among Chamorro migrants from Guam. Annals of Neurology 8:612–19. doi:10.1002/ana.410080612.
  • Garruto, R. M., S. K. Shankar, R. Yanagihara, A. M. Salazar, H. L. Amyx, and D. C. Gajdusek. 1989. Low-calcium, high-aluminum diet-induced motor neuron pathology in cynomolgus monkeys. Acta Neuropathologica 78:210–19. doi:10.1007/BF00688211.
  • Garruto, R. M., C. Swyt, C. E. Fiori, R. Yanagihara, and D. C. Gajdusek. 1985a. Intraneuronal deposition of calcium and aluminum in amyotrophic lateral sclerosis of Guam. Lancet 2:1353. doi:10.1016/S0140-6736(85)92642-X.
  • Garruto, R. M., C. Swyt, R. Yanagihara, C. E. Fiori, and D. C. Gajdusek. 1986. Intraneuronal co-localization of silicon with calcium and aluminum in amyotrophic lateral sclerosis and Parkinsonism with dementia of Guam. The New England Journal of Medicine 315:711–12. doi:10.1056/NEJM198609113151115.
  • Garruto, R. M., R. Yanagihara, and D. C. Gajdusek. 1985b. Disappearance of high-incidence amyotrophic lateral sclerosis and Parkinsonism-dementia on Guam. Neurology 35:193–98. doi:10.1212/WNL.35.2.193.
  • Garruto, R. M., R. Yanagihara, D. C. Gajdusek, and D. M. Arion. 1984b. Concentrations of heavy metals and essential minerals in garden soil and drinking water in the western Pacific. In Amyotrophic lateral sclerosis in Asia and Oceania, eds. C. K-M, and Y. Yase, 343–53. Taipei, Taiwan: National Taiwan University.
  • Garruto, R. M., and Y. Yase. 1986. Neurodegenerative disorders of the Western Pacific - The search for mechanisms of pathogenesis. Trend Neuroscience 9:368–74. doi:10.1016/0166-2236(86)90116-5.
  • Gellein, K., R. M. Garruto, T. Syversen, T. E. Sjobakk, and T. P. Flaten. 2003. Concentrations of Cd, Co, Cu, Fe, Mn, Rb, V, and Zn in formalin-fixed brain tissue in amyotrophic lateral sclerosis and Parkinsonism-dementia complex of Guam determined by high-resolution ICP-MS. Biological Trace Element Research 96:39–60. doi:10.1385/BTER:96:1-3:39.
  • Geser, F., M. J. Winton, L. K. Kwong, Y. Xu, S. X. Xie, L. M. Igaz, R. M. Garruto, D. P. Perl, D. Galsko, V. M. Lee, and J. Q. Trojanowski. 2008. Pathological TDP-43 in Parkinsonism-demetia complex and amyotrophic lateral sclerosis of Guam. Acta Neuropathologica 115:133–45. doi:10.1007/s00401-007-0257-y.
  • Gibbs, C. J.Jr., and D. C. Gajdusek. 1972. Amyotrophic lateral sclerosis, Parkinson’s disease, and the Amyotrophic lateral sclerosis-Parkinsonism dementia Complex on Guam: A review and summary of attempts to demonstrate infection as the etiology. Journal Clinical Pathologists 25 Supplement (R College Pathol) 132–40. doi:10.1136/jcp.s3-6.1.132.
  • Glover, W. B., S. A. Cohen, and S. J. Murch. 2015. Liquid chromatography and mass spectrometry for the analysis of n-beta-methylamino-l-alanine with 6-aminoquinolyl-n-hydroxysuccinimidyl carbamate. Advancement Protocols Oxidative Stress Iii 1208:379–91.
  • Glover, W. B., D. C. Mash, and S. J. Murch. 2014. The natural non-protein amino acid N-beta-methylamino-L-alanine (BMAA) is incorporated into protein during synthesis. Amino Acids 46:2553–59. doi:10.1007/s00726-014-1812-1.
  • Griapon, Y., and A. Togodly. 2008. Research report on neurodegenerative diseases in Bade, Edera district, Mappi, Papua, Indonesia: Case studies on Auyu and Jakay people, vol. 9, 153–58. Kyoto University Bhutan Friendship Program. Kyoto: Field Institute of Southeast Asian Studies, Kyoto University.
  • Hanlon, S. D., and J. C. Steele. 1993. An unusual retinal pigment epitheliopathy endemic to the island of Guam. Opthomol Vision Sciences 70:854–59. doi:10.1097/00006324-199310000-00014.
  • Hanrieder, J., L. Gerber, A. Persson Sandelius, E. B. Brittebo, A. G. Ewing, and O. Karlsson. 2014. High resolution metabolite imaging in the hippocampus following neonatal exposure to the environmental toxin BMAA using ToF-SIMS. ACS Chemical Neuroscience 5:568–75. doi:10.1021/cn500039b.
  • Hill, A. B. 1965. The environment and disease: Association or causation? Proceedings of the Royal Society of Medicine 58:295–300.
  • Hirano, A., L. T. Kurland, R. S. Krooth, and S. Lessell. 1961b. Parkinsonism dementia complex, an endemic disease on the island of Guam. I. Clinical features. Brain 84:642–61. doi:10.1093/brain/84.4.642.
  • Hirano, A., N. Malamud, T. S. Elizan, and L. T. Kurland. 1966. Amyotrophic lateral sclerosis and Parkinsonism dementia complex on Guam. Further pathologic studies. Archives of Neurology 15:35–51. doi:10.1001/archneur.1966.00470130039004.
  • Hirano, A., N. Malamud, and L. T. Kurland. 1961a. Parkinsonism dementia complex, an endemic disease on the island of Guam. II. Pathological features. Brain 84:662–79. doi:10.1093/brain/84.4.662.
  • Hirano, A., and H. M. Zimmerman. 1962. Alzheimer’s neurofibrillary changes. A topographic study. Archives of Neurology 7:227–42. doi:10.1001/archneur.1962.04210030065009.
  • Hirata, Y. 2008. Walking in coastal jungle of West New Guinea–landscape, neurodegenerative disease, totem spirits and medical science. Report No. 9, Kyoto University Bhutan Friendship Program, Kyoto.
  • Hirono, I., and C. Shibuya. 1967. Induction of a neurological disorder by cycasin in mice. Nature 216:1311–12. doi:10.1038/2161311a0.
  • Hirono, I., C. Shibuya, and K. Hayashi. 1969. Induction of a cerebellar disorder with cycasin in newborn mice and hamsters. Proceedings of the Society for Experimental Biology and Medicine 131:593–99. doi:10.3181/00379727-131-33933.
  • Hof, P. R., D. P. Perl, A. J. Loerzel, and J. H. Morrison. 1991. Neurofibrillary tangle distribution in the cerebral cortex of Parkinsonism-dementia cases from Guam: Differences with Alzheimer’s disease. Brain Research 564:306–13. doi:10.1016/0006-8993(91)91467-F.
  • Hof, P. R., D. P. Perl, A. J. Loerzel, J. C. Steele, and J. H. Morrison. 1994. Amyotrophic lateral sclerosis and Parkinsonism-dementia from Guam: Differences in neurofibrillary tangle distribution and density in the hippocampal formation and neocortex. Brain Research 650:107–16. doi:10.1016/0006-8993(94)90212-7.
  • Hong, S. H., Y. C. Kwon, and M. C. Jewett. 2014. Non-standard amino acid incorporation into proteins using Escherichia coli cell-free protein synthesis. Frontiers Chemical 2:34. doi:10.3389/fchem.2014.00034.
  • Hynd, M. R., H. L. Scott, and P. R. Dodd. 2004. Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease. Neurochemistry International 45:583–95. doi:10.1016/j.neuint.2004.03.007.
  • Ikemoto, A., A. Hirano, and I. Akiguchi. 2000. Neuropathology of Amyotrophic lateral sclerosis with extra-motor system degeneration: Characteristics and differences in the molecular pathology between ALS with dementia and Guamanian ALS. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 1:97–104. doi:10.1080/14660820050515395.
  • Jiang, L., J. Eriksson, S. Lage, S. Jonasson, S. Shams, M. Mehine, et al. 2014a. Diatoms: A novel source for the neurotoxin BMAA in aquatic environments. PLoS One 9:e84578. doi:10.1371/journal.pone.0084578.
  • Jiang, L., E. Johnston, K. M. Aberg, U. Nilsson, and L. L. Ilag. 2013. Strategy for quantifying trace levels of BMAA in cyanobacteria by LC/MS/MS. Analytical and Bioanalytical Chemistry 405:1283–92. doi:10.1007/s00216-012-6550-1.
  • Jiang, L., N. Kiselova, J. Rosen, and L. L. Ilag. 2014b. Quantification of neurotoxin BMAA (beta-N-methylamino-L-alanine) in seafood from Swedish markets. Scientific Reports 4:6931. doi:10.1038/srep06931.
  • Jiao, Y., Q. Chen, X. Chen, X. Wang, X. Liao, L. Jiang, et al. 2014. Occurrence and transfer of a cyanobacterial neurotoxin beta-methylamino-L-alanine within the aquatic food webs of Gonghu Bay (Lake Taihu, China) to evaluate the potential human health risk. The Science of the Total Environment 468-469:457–63. doi:10.1016/j.scitotenv.2013.08.064.
  • Johnson, H. E., S. R. King, S. A. Banack, C. Webster, W. J. Callanaupa, and P. A. Cox. 2008. Cyanobacteria (Nostoc commune) used as a dietary item in the Peruvian highlands produce the neurotoxic amino acid BMAA. Journal of Ethnopharmacology 118:159–65. doi:10.1016/j.jep.2008.04.008.
  • Jonasson, S., J. Eriksson, L. Berntzon, Z. Spacil, L. L. Ilag, L. O. Ronnevi, et al. 2010. Transfer of a cyanobacterial neurotoxin within a temperate aquatic ecosystem suggests pathways for human exposure. Proceedings of the National Academy of Sciences of the United States of America 107:9252–57. doi:10.1073/pnas.0914417107.
  • Karlsson, O., A. L. Berg, J. Hanrieder, G. Arnerup, A. K. Lindstrom, and E. B. Brittebo. 2015. Intracellular fibril formation, calcification, and enrichment of chaperones, cytoskeletal, and intermediate filament proteins in the adult hippocampus CA1 following neonatal exposure to the non-protein amino acid BMAA. Archives of Toxicology 89:423–36. doi:10.1007/s00204-014-1262-2.
  • Karlsson, O., A. L. Berg, A. K. Lindstrom, J. Hanrieder, G. Arnerup, E. Roman, et al. 2012. Neonatal exposure to the cyanobacterial toxin BMAA induces changes in protein expression and neurodegeneration in adult hippocampus. Toxicological Sciences 130:391–404. doi:10.1093/toxsci/kfs241.
  • Karlsson, O., J. Bergquist, and M. Andersson. 2014a. Quality measures of imaging mass spectrometry aids in revealing long-term striatal protein changes induced by neonatal exposure to the cyanobacterial toxin beta-N-methylamino-L-alanine (BMAA). Molecular & Cellular Proteomics 13:93–104. doi:10.1074/mcp.M113.031435.
  • Karlsson, O., L. Jiang, M. Andersson, L. L. Ilag, and E. B. Brittebo. 2014b. Protein association of the neurotoxin and non-protein amino acid BMAA (beta-N-methylamino-L-alanine) in the liver and brain following neonatal administration in rats. Toxicology Letters 226:1–5. doi:10.1016/j.toxlet.2014.01.027.
  • Karlsson, O., K. Kultima, H. Wadensten, A. Nilsson, E. Roman, P. E. Andren, et al. 2013. Neurotoxin-induced neuropeptide perturbations in striatum of neonatal rats. Journal of Proteome Research 12:1678–90. doi:10.1021/pr3010265.
  • Karlsson, O., N. G. Lindquist, E. B. Brittebo, and E. Roman. 2009a. Selective brain uptake and behavioral effects of the cyanobacterial toxin BMAA (beta-N-methylamino-L-alanine) following neonatal administration to rodents. Toxicological Sciences 109:286–95. doi:10.1093/toxsci/kfp062.
  • Karlsson, O., E. Roman, A. L. Berg, and E. B. Brittebo. 2011. Early hippocampal cell death, and late learning and memory deficits in rats exposed to the environmental toxin BMAA (beta-N-methylamino-L-alanine) during the neonatal period. Behavioural Brain Research 219:310–20. doi:10.1016/j.bbr.2011.01.056.
  • Karlsson, O., E. Roman, and E. B. Brittebo. 2009b. Long-term cognitive impairments in adult rats treated neonatally with beta-N-methylamino-L-alanine. Toxicological Sciences 112:185–95. doi:10.1093/toxsci/kfp196.
  • Kato, S., A. Hirano, J. F. Llena, H. Ito, and S. H. Yen. 1992. Ultrastructural identification of neurofibrillary tangles in the spinal cords in Guamanian amyotrophic lateral sclerosis and Parkinsonism dementia complex on Guam. Acta Neuropathologica 83:277–82. doi:10.1007/BF00296790.
  • Khabazian, I., J. S. Bains, D. E. Williams, J. Cheung, J. M. Wilson, B. A. Pasqualotto, et al. 2002. Isolation of various forms of sterol beta-D-glucoside from the seed of Cycas circinalis: Neurotoxicity and implications for ALS-Parkinsonism dementia complex. Journal of Neurochemistry 82:516–28. doi:10.1046/j.1471-4159.2002.00976.x.
  • Kihira, T., K. Okamoto, S. Yoshida, T. Kondo, K. Iwai, S. Wada, Y. Kajimoto, T. Kondo, Y. Kokubo, and Kuzuhara. 2013. Environmental characteristics and oxidative stress of inhabitants and patients with Amyotrophic lateral sclerosis in a high-incidence area on the Kii Peninsula, Japan. Internal Medicine 52:1479–86. doi:10.2169/internalmedicine.52.9521.
  • Kihira, T., S. Yoshida, Y. Yase, S. Ono, and T. Kondo. 2002. Chronic low-Ca/Mg high-Al diet induces neuronal loss. Neuropathology 22:171–79. doi:10.1046/j.1440-1789.2002.00441.x.
  • Kimura, K., Y. Yase, and Y. Higashi. 1963. Epidemiological and geomedical studies on amyotrophic lateral sclerosis. Diseases of the Nervous System 24:155–59.
  • Kisby, G. E., M. Ellison, and P. S. Spencer. 1992. Content of the neurotoxins cycasin (methylazoxymethanol beta-D-glucoside) and BMAA (beta-N-methylamino-L-alanine) in cycad flour prepared by Guam Chamorros. Neurology 42:1336–40. doi:10.1212/WNL.42.7.1336.
  • Kisby, G. E., R. C. Fry, M. R. Lasarev, T. K. Bammler, R. P. Beyer, M. Churchwell, D. R. Doerge, L. B. Meira, V. S. Palmer, A. L. Ramos-Crawford, X. Ren, R. C. Sullivan, T. J. Kavanagh, L. D. Samson, H. Zarbl, and P. S. Spencer. 2011. The cycad genotoxin MAM modulates brain cellular pathways involved in neurodegenerative disease and cancer in a DNA damage-linked manner. PLoS One 6:e20911. doi:10.1371/journal.pone.0020911.
  • Kisby, G. E., and P. S. Spencer. 2011. Is neurodegenerative disease a long-latency response to early-life genotoxin exposure? International Journal of Environmental Research and Public Health 8:3889–921. doi:10.3390/ijerph8103889.
  • Koerner, D. R. 1952. Amyotrophic lateral sclerosis on Guam. Annals of Internal Medicine 37:1204–20. doi:10.7326/0003-4819-37-6-1204.
  • Kokubo, Y., K. Ito, T. Fukunaga, H. Matsubara, and S. Kuzuhara. 2006. Pigmentary retinopathy of ALS/PDC in Kii. Ophthalmology 113:e2111–e2112. doi:10.1016/j.ophtha.2006.07.002.
  • Kokubo, Y., K. Ito, and S. Kuzuhara. 2003. Ophthalmomyiasis-like pigmentary retinopathy in ALS/PDC in the Kii Peninsula of Japan. Neurology 60:1725–26. doi:10.1212/01.WNL.0000061487.16841.72.
  • Kokubo, Y., and S. Kuzuhara. 2001. Neurological and neuropathological studies of Amyotrophic lateral sclerosis/Parkinsonism dementia complex in the Kii Peninsula of Japan. Rinsho Shinkeigaku 41:769–74.
  • Kokubo, Y., and S. Kuzuhara. 2003. Neuroradiological study of patients with amyotrophic lateral sclerosis and Parkinsonism-dementia complex on the Kii Peninsula of Japan. Archives of Neurology 60:1257–61. doi:10.1001/archneur.60.9.1257.
  • Kruger, T., B. Monch, S. Oppenhauser, and B. Luckas. 2010. LC-MS/MS determination of the isomeric neurotoxins BMAA (beta-N-methylamino-L-alanine) and DAB (2,4-diaminobutyric acid) in cyanobacteria and seeds of Cycas revoluta and Lathyrus latifolius. Toxicon 55:547–57. doi:10.1016/j.toxicon.2009.10.009.
  • Kubo, T., N. Kato, K. Hosoya, and K. Kaya. 2008. Effective determination method for a cyanobacterial neurotoxin, beta-N-methylamino-L-alanine. Toxicon 51:1264–68. doi:10.1016/j.toxicon.2008.02.015.
  • Kumamoto, T., S. Nakagawa, C. Suematsu, E. Shimizu, Y. Yata, and T. Hirohata. 1975. Experimental calcium-magnesium deficiency in rats - Chemical and histochemical study. Acta Histochemica et Cytochemica 8:294–303. doi:10.1267/ahc.8.294.
  • Kurland, L. T. 1961. Parkinsonism-dementia complex, an endemic disease on the island of Guam. Transactions of the American Neurological Association 86:115–20.
  • Kurland, L. T. 1972. An appraisal of the neurotoxicity of cycad and the etiology of amyotrophic lateral sclerosis on Guam. Federation Proceedings 31:1540–42.
  • Kurland, L. T., and D. W. Mulder 1954a. Epidemiologic investigations of amyotrophic lateral sclerosis. II. Preliminary report on geographic distribution and special reference to the Mariana Islands, including clinical and pathologic observations. Neurology 4: 438–48. doi:10.1212/WNL.4.6.438.
  • Kurland, L. T., and D. W. Mulder. 1954b. Epidemiologic investigations of amyotrophic lateral sclerosis. I. Preliminary report on geographic distribution, with special reference to the Mariana Islands, including clinical and pathologic observations. Neurology 4:355–78. doi:10.1212/WNL.4.5.355.
  • Kuzuhara, S. 2007. Revisit to Kii ALS–the innovated concept of ALS-Parkinsonism dementia complex, clinicopathological features, epidemiology and etiology. Brain and Nerve 59:1065–74.
  • Kuzuhara, S., Y. Kokubo, R. Sasaki, Y. Narita, T. Yabana, M. Hasegawa, and T. Iwatsubo. 2001. Familial amyotrophic lateral sclerosis and Parkinsonism dementia complex of the Kii Peninsula of Japan: Clinical and neuropathological study and tau analysis. Annals of Neurology 49:501–11. doi:10.1002/(ISSN)1531-8249.
  • Lage, S., H. Annadotter, U. Rasmussen, and S. Rydberg. 2015. Biotransfer of beta-N-methylamino-l-alanine (BMAA) in a eutrophicated freshwater lake. Marine Drugs 13:1185–201. doi:10.3390/md13031185.
  • Lage, S., A. Burian, U. Rasmussen, P. R. Costa, H. Annadotter, and A. Godhe. 2016. BMAA extraction of cyanobacteria samples: Which method to choose? Environmental Science and Pollution Research International 23:338–50. doi:10.1007/s11356-015-5266-0.
  • Lage, S., P. R. Costa, T. Moita, J. Eriksson, U. Rasmussen, and S. J. Rydberg. 2014. BMAA in shellfish from two Portuguese transitional water bodies suggests the marine dinoflagellate Gymnodinium catenatum as a potential BMAA source. Aquatic Toxicology 152:131–38. doi:10.1016/j.aquatox.2014.03.029.
  • Laqueur, G. L., and H. Matsumoto. 1966. Neoplasms in female Fischer rats following intraperitoneal injection of methylazoxy-methanol. Journal of the National Cancer Institute 37:217–32.
  • Laqueur, G. L., O. Mickelsen, M. G. Whiting, and L. T. Kurland. 1963. Carcinogenic properties of nuts from Cycas circinalis L. indigenous to Guam. Journal of the National Cancer Institute 31:919–51.
  • Laqueur, G. L., and M. Spatz. 1968. Toxicology of cycasin. Cancer Research 28:2262–67.
  • Lau, C. 2012. Perfluorinated compounds. EXS 101:47–86.
  • Leblanc, B., S. Jezequel, T. Davies, G. Hanton, and C. Taradach. 1998. Binding of drugs to eye melanin is not predictive of ocular toxicity. Regulatory Toxicology and Pharmacology 28:124–32. doi:10.1006/rtph.1998.1243.
  • Lee, M. H., and A. Rabe. 1992. Premature decline in Morris water maze performance of aging micrencephalic rats. Neurotoxicology and Teratology 14:383–92. doi:10.1016/0892-0362(92)90048-F.
  • Lemere, C. A., A. Beierschmitt, M. Iglesias, E. T. Spooner, J. K. Bloom, J. F. Leverone, J. B. Zheng, T. J. Seabrook, D. Louard, D. Li, D. J. Selkoe, R. M. Palmour, and F. R. Ervin. 2004. Alzheimer’s disease A beta vaccine reduces central nervous system A beta levels in a non-human primate, the Caribbean vervet. The American Journal of Pathology 165:283–97. doi:10.1016/S0002-9440(10)63296-8.
  • Lemke, T. O. 1992. History of fruit bat use, research, and, protection in the Northern Mariana Islands. Biologic Reports, United States Fish and Wildlife Service 90:135–42.
  • Lepore, F. E., J. C. Steele, T. A. Cox, G. Tillson, D. B. Calne, R. C. Duvoisin, L. Lavine, and J. V. McDarby. 1988. Supranuclear disturbances of ocular motility in Lytico-Bodig. Neurology 38:1849–53. doi:10.1212/WNL.38.12.1849.
  • Li, A., H. Fan, F. Ma, P. McCarron, K. Thomas, X. Tang, et al. 2012. Elucidation of matrix effects and performance of solid-phase extraction for LC-MS/MS analysis of beta-N-methylamino-L-alanine (BMAA) and 2,4-diaminobutyric acid (DAB) neurotoxins in cyanobacteria. The Analyst 137:1210–19. doi:10.1039/c2an15887f.
  • Lim, R. 2012. BMAA neurotoxin found in shark fins linked to Alzheimer’s Disease. Asian Scientist.
  • Lindblad, P. 1990. Nitrogen and carbon metabolism in coralloid roots of cycads. Memoirs of the New York Botanical Garden 57:104–13.
  • Loftfield, R. B. 1963. The frequency of errors in protein biosynthesis. The Biochemical Journal 89:82–92. doi:10.1042/bj0890082.
  • Lucas, R. B., and A. J. McMichael. 2005. Association and causation: Evaluating risks between “environment and disease. Bulletin WHO 83:792–95.
  • Ludolph, A. C., J. Kassubek, B. G. Landwehrmeyer, E. Mandelkow, E. M. Mandelkow, and D. J. Burn. 2009. Tauopathies with Parkinsonism: Clinical spectrum, neuropathologic basis, biological markers, and treatment options. European Journal of Neurology 16:297–309. doi:10.1111/j.1468-1331.2008.02513.x.
  • Ly, P. T., S. Singh, and C. A. Shaw. 2007. Novel environmental toxins: Steryl glycosides as a potential etiological factor for age-related neurodegenerative diseases. Journal of Neuroscience Research 85:231–37. doi:10.1002/(ISSN)1097-4547.
  • Madeira, C., M. V. Lourenco, C. Vargas-Lopes, C. K. Suemoto, C. O. Brandao, T. Reis, R. E. P. Leite, J. Laks, W. Jacob-Filho, C. A. Pasqualucci, L. T. Grinberg, S. T. Ferreira, and R. Panizzutti. 2015. D-serine levels in Alzheimer’s disease: Implications for novel biomarker development. Translational Psychiatry 5:e561. doi:10.1038/tp.2015.52.
  • Malamud, N., A. Hirano, and L. T. Kurland. 1961. Pathoanatomic changes in amyotrophic lateral sclerosis on Guam. Special reference to the occurrence of neurofibrillary changes. Archives of Neurology 5:401–15. doi:10.1001/archneur.1961.00450160051003.
  • Marler, T. E., L. R. Snyder, and C. A. Shaw. 2010. Cycas micronesica (Cycadales) plants devoid of endophytic cyanobacteria increase in beta-methylamino-L-alanine. Toxicon 56:563–68. doi:10.1016/j.toxicon.2010.05.015.
  • Matsumoto, S., A. Hirano, and S. Goto. 1990. Spinal-cord neurofibrillary tangles of Guamanian amyotrophic lateral sclerosis and Parkinsonism dementia complex - An immunohistochemical study. Neurology 40:975–79. doi:10.1212/WNL.40.6.975.
  • McAuliffe, K. 2011. There’s something in the water. Discover 30:41–46.
  • McCarron, P., A. C. Logan, S. D. Giddings, and M. A. Quilliam. 2014. Analysis of beta-N-methylamino-L-alanine (BMAA) in spirulina-containing supplements by liquid chromatography-tandem mass spectrometry. Aquatic Biosystems 10:5. doi:10.1186/2046-9063-10-5.
  • McGeer, P. L., C. Schwab, E. G. McGeer, R. L. Haddock, and J. C. Steele. 1997. Familial nature and continuing morbidity of the amyotrophic lateral sclerosis-Parkinsonism dementia complex of Guam. Neurology 49:400–09. doi:10.1212/WNL.49.2.400.
  • McGeer, P. L., and J. C. Steele. 2011. The ALS/PDC syndrome of Guam: Potential biomarkers for an enigmatic disorder. Progress in Neurobiology 95:663–69. doi:10.1016/j.pneurobio.2011.04.001.
  • McGorum, B. C., R. S. Pirie, L. Glendinning, G. McLachlan, J. S. Metcalf, S. A. Banack, P. A. Cox, and G. A. Codd. 2015. Grazing livestock are exposed to terrestrial cyanobacteria. Veterinary Research 46:16.
  • Metcalf, J. S., S. A. Banack, K. Kotut, L. Krienitz, and G. A. Codd. 2013. Amino acid neurotoxins in feathers of the Lesser Flamingo. Phoeniconaias Minority Chemosphere 90:835–39. doi:10.1016/j.chemosphere.2012.09.094.
  • Metcalf, J. S., S. A. Banack, J. Lindsay, L. F. Morrison, P. A. Cox, and G. A. Codd. 2008. Co-occurrence of beta-N-methylamino-L-alanine, a neurotoxic amino acid with other cyanobacterial toxins in British waterbodies, 1990-2004. Environmental Microbiology 10:702–08. doi:10.1111/j.1462-2920.2007.01492.x.
  • Metcalf, J. S., S. A. Banack, R. Richer, and P. A. Cox. 2015. Neurotoxic amino acids and their isomers in desert environments. Journal of Arid Environments 112:140–44. doi:10.1016/j.jaridenv.2014.08.002.
  • Miklossy, J., J. C. Steele, S. Yu, S. McCall, G. Sandberg, E. G. McGeer, and P. L. McGeer. 2008. Enduring involvement of tau, beta-amyloid, alpha-synuclein, ubiquitin and TDP-43 pathology in the amyotrophic lateral sclerosis/Parkinsonism dementia complex of Guam (ALS/PDC). Acta Neuropathologica 116:625–37. doi:10.1007/s00401-008-0439-2.
  • Mimuro, M., Y. Kokubo, and S. Kuzuhara. 2007. Similar topographical distribution of neurofibrillary tangles in Amyotrophic lateral sclerosis and Parkinsonism dementia complex in people living in the Kii Peninsula of Japan suggests a single tauopathy. Acta Neuropathologica 113:653–58. doi:10.1007/s00401-007-0197-6.
  • Mondo, K., W. Broc Glover, S. J. Murch, G. Liu, Y. Cai, D. A. Davis, and D. C. Mash. 2014. Environmental neurotoxins beta-N-methylamino-L-alanine (BMAA) and mercury in shark cartilage dietary supplements. Food and Chemical Toxicology 70:26–32. doi:10.1016/j.fct.2014.04.015.
  • Mondo, K., N. Hammerschlag, M. Basile, J. Pablo, S. A. Banack, and D. C. Mash. 2012. Cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) in shark fins. Marine Drugs 10:509–20. doi:10.3390/md10020509.
  • Monson, C. S., S. A. Banack, and P. A. Cox. 2003. Conservation implications of Chamorro consumption of flying foxes as a possible cause of amyotrophic lateral sclerosis-Parkinsonism dementia complex in Guam. Conservation Biology 17:678–86. doi:10.1046/j.1523-1739.2003.02049.x.
  • Montine, T. J., K. Li, D. P. Perl, and D. Galasko. 2005. Lack of beta-methylamino-l-alanine in brain from controls, AD, or Chamorros with PDC. Neurology 65:768–69. doi:10.1212/01.wnl.0000174523.62022.52.
  • Morris, H. R., S. Al-Sarraj, C. Schwab, K. Gwinn-Hardy, J. Perez-Tur, N. W. Wood, J. Hardy, A. J. Lees, P. L. McGeer, S. E. Daniel, and J. C. Steele. 2001. A clinical and pathological study of motor neurone disease on Guam. Brain 124:2215–22. doi:10.1093/brain/124.11.2215.
  • Morris, H. R., J. C. Steele, R. Crook, F. Wavrant-De Vrieze, L. Onstead-Cardinale, K. Gwinn-Hardy, N. W. Wood, M. Farrer, A. J. Lees, P. L. McGeer, T. Siddique, J. Hardy, and J. Perez-Tur. 2004. Genome-wide analysis of the Parkinsonism dementia complex of Guam. Archives of Neurology 61:1889–97. doi:10.1001/archneur.61.12.1889.
  • Murakami, N. 1999. Parkinsonism dementia complex on Guam - Overview of clinical aspects. Journal of Neurology 246:16–18. doi:10.1007/BF03161077.
  • Murch, S. J., P. A. Cox, and S. A. Banack. 2004a. A mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in Guam. Proceedings of the National Academy of Sciences of the United States of America 101:12228–31. doi:10.1073/pnas.0404926101.
  • Murch, S. J., P. A. Cox, S. A. Banack, J. C. Steele, and O. W. Sacks. 2004b. Occurrence of beta-methylamino-L-alanine (BMAA) in ALS/PDC patients from Guam. Acta Neurologica Scandinavica 110:267–69. doi:10.1111/ane.2004.110.issue-4.
  • Nakagawa, S., S. Yoshida, C. Suematsu, E. Shimizu, T. Hirohata, T. Kumamoto, Y. Yase, K. Kawai, and S. Iwata. 1977. The calcium-magnesium-deficient rat: A study on the distribution of calcium in the spinal cord using the electron probe microanalyser. Experientia 33:1225–26. doi:10.1007/BF01922343.
  • Nakao, T., O. Aozasa, S. Ohta, and H. Miyata. 2002. Assessment of human exposure to PCDDs, PCDFs and Co-PCBs using hair as a human pollution indicator sample I: Development of analytical method for human hair and evaluation for exposure assessment. Chemosphere 48:885–96. doi:10.1016/S0045-6535(02)00156-X.
  • Nishida, K., A Kobayashi, and T. Nagahama. 1955. A new toxic glycoside of Cycas revoluta Thunb. Part I. Isolation and the structure of cycasin. Bulletin Agricultural Chemical Social Japan 19:77–83.
  • Obendorf, P., and P. S. Spencer. 2000. Medicinal use of cycads (Cycas sp.) in New Guinea and neighbouring islands. Perspectives in Human Biology 5:31–41.
  • Okle, O., K. Stemmer, U. Deschl, and D. R. Dietrich. 2013. L-BMAA induced ER stress and enhanced caspase 12 cleavage in human neuroblastoma SH-SY5Y cells at low nonexcitotoxic concentrations. Toxicological Sciences 131:217–24. doi:10.1093/toxsci/kfs291.
  • Okumiya, K., M. Fujisawa, M. Ishine, T. Tada, R. Sakamoto, Y. Hirata, E. G. Del Saz, Y. Griapon, N. Sanggenafa, A. Togodly, A. L. Rantetampang, Y. Kokubo, S. Kuzuhara, and K. Matsubayashi. 2008. Neurodegenerative diseases in West New-Guinea. Himalayan Study Monographs 9:141–45.
  • Oyanagi, K., T. Makifuchi, T. Ohtoh, K. M. Chen, T. van der Schaaf, D. C. Gajdusek, T. N. Chase, and F. Ikuta. 1994. Amyotrophic lateral sclerosis of Guam: The nature of the neuropathological findings. Acta Neuropathologica 88:405–12. doi:10.1007/BF00389491.
  • Pablo, J., S. A. Banack, P. A. Cox, T. E. Johnson, S. Papapetropoulos, W. G. Bradley, A. Buck, and D. C. Mash. 2009. Cyanobacterial neurotoxin BMAA in ALS and Alzheimer’s Disease. Acta Neurologica Scandinavica 120:216–25. doi:10.1111/j.1600-0404.2008.01150.x.
  • Papageorgiou, J., B. Nicholson, W. Wickramasinghe, and C. Kapralos. 2009. BMAA in potable waters: An international assessment of exposure levels. WQRA Research Report 65. Adelaide: Water Quality Research Limited.
  • Papapetropoulos, S. 2007. Is there a role for naturally occurring cyanobacterial toxins in neurodegeneration? The beta-N-methylamino-L-alanine (BMAA) paradigm. Neurochemistry International 50:998–1003. doi:10.1016/j.neuint.2006.12.011.
  • Partensky, F., W. R. Hess, and D. Vaulot. 1999. Prochlorococcus, a marine photosynthetic prokaryote of global significance. Microbiology and Molecular Biology Reviews 63:106–27.
  • Perez-Tur, J., L. Buee, H. R. Morris, S. C. Waring, L. Onstead, F. Wavrant-De Vrieze, R. Crook, V. Buee-Scherrer, P. R. Hof, R. C. Petersen, P. L. McGeer, A. Delacourte, M. Hutton, T. Siddique, J. E. Ahlskog, J. Hardy, and J. C. Steele. 1999. Neurodegenerative diseases of Guam: Analysis of Tau. Neurology 53:411–13. doi:10.1212/WNL.53.2.411.
  • Perkins, H. R., and C. S. Cummins. 1964. Chemical structure of bacterial cell walls. Ornithine and 2,4-diaminobutyric acid as components of the cell walls of plant pathogenic corynebacteria. Nature 201:1105–07. doi:10.1038/2011105a0.
  • Perl, D. P., D. C. Gajdusek, R. M. Garruto, R. T. Yanagihara, and C. J. Gibbs. 1982. Intraneuronal aluminum accumulation in Amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam. Science 217:1053–55. doi:10.1126/science.7112111.
  • Perry, T. L., C. Bergeron, A. J. Biro, and S. Hansen. 1989. Beta-N-methylamino-L-alanine. Chronic oral administration is not neurotoxic to mice. Journal of the Neurological Sciences 94:173–80. doi:10.1016/0022-510X(89)90227-X.
  • Perry, T. L., C. Bergeron, J. C. Steele, D. R. McLachlan, and S. Hansen. 1990. Brain amino acid contents are dissimilar in sporadic and Guamanian amyotrophic lateral sclerosis. Journal of the Neurological Sciences 99:3–8. doi:10.1016/0022-510X(90)90194-R.
  • Piccardo, P., R. Yanagihara, R. M. Garruto, C. J. GibbsJr., and D. C. Gajdusek. 1988. Histochemical and X-ray microanalytical localization of aluminum in Amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam. Acta Neuropathologica 77:1–4. doi:10.1007/BF00688235.
  • Plato, C. C., M. T. Cruz, and L. T. Kurland. 1969. Amyotrophic lateral sclerosis-Parkinsonism dementia complex of Guam: Further genetic investigations. American Journal Human Genetics 21:133–41.
  • Plato, C. C., D. Galasko, R. M. Garruto, M. Plato, A. Gamst, U. K. Craig, J. M. Torres, and W. Wiederholt. 2002. ALS and PDC of Guam: Forty-year follow-up. Neurology 58:765–73. doi:10.1212/WNL.58.5.765.
  • Plato, C. C., R. M. Garruto, D. Galasko, U. K. Craig, M. Plato, A. Gamst, J. M. Torres, and W. Wiederholt. 2003. Amyotrophic lateral sclerosis and Parkinsonism dementia complex of Guam: Changing incidence rates during the past 60 years. American Journal of Epidemiology 157:149–57. doi:10.1093/aje/kwf175.
  • Pragst, F., and M. A. Balikova. 2006. State of the art in hair analysis for detection of drug and alcohol abuse. Chimica Acta 370:17–49. doi:10.1016/j.cca.2006.02.019.
  • Rao, S. L., P. R. Adiga, and P. S. Sarma. 1964. The isolation and characterization of beta-N-oxalyl-L-alpha,beta-diaminopropionic Acid: A neurotoxin from the seeds of Lathyrus sativus. Biochemistry 3:432–36. doi:10.1021/bi00891a022.
  • Reed, D., D. Labarthe, K. M. Chen, and R. Stallones. 1987. A cohort study of Amyotrophic lateral sclerosis and Parkinsonism-dementia on Guam and Rota. American Journal of Epidemiology 125:92–100. doi:10.1093/oxfordjournals.aje.a114515.
  • Reed, D. M., and J. A. Brody. 1975. Amyotrophic lateral sclerosis and Parkinsonism-dementia on Guam, 1945-1972. I. Descriptive epidemiology. American Journal of Epidemiology 101:287–301. doi:10.1093/oxfordjournals.aje.a112097.
  • Reed, D. M., J. M. Torres, and J. A. Brody. 1975. Amyotrophic lateral sclerosis and Parkinsonism-dementia on Guam, 1945-1972. II. Familial and genetic studies. American Journal of Epidemiology 101:302–10. doi:10.1093/oxfordjournals.aje.a112098.
  • Reiff, D. M., R. Spathis, C. W. Chan, M. G. Vilar, K. Sankaranarayanan, D. Lynch, E. Ehrlich, S. Kerath, R. Chowdhury, L. Robinowitz, J. Koji Lum, and R. M. Garruto. 2011. Inherited and somatic mitochondrial DNA mutations in Guam amyotrophic lateral sclerosis and Parkinsonism-dementia. Neurological Sciences 32:883–92. doi:10.1007/s10072-011-0735-9.
  • Reveillon, D., E. Abadie, V. Sechet, L. Brient, V. Savar, M. Bardouil, P. Hess, and Z. Amzil. 2014. Beta-N-methylamino-L-alanine: LC-MS/MS optimization, screening of cyanobacterial strains and occurrence in shellfish from Thau, a French Mediterranean lagoon. Marine Drugs 12:5441–67. doi:10.3390/md12115441.
  • Reveillon, D., E. Abadie, V. Sechet, E. Masseret, P. Hess, and Z. Amzil. 2015. β-N-methylamono-L-alanine (BMAA) and its isomers: Distribution in different food web compartments of Thau lagoon, French Mediterranean Sea. Marine Environmental Research 110:8–18. doi:10.1016/j.marenvres.2015.07.015.
  • Reveillon, D., V. Sechet, P. Hess, and Z. Amzil. 2016. Production of BMAA and DAB by diatoms (Phaeodactylum tricornutum, Chaetoceros sp., Chaetoceros calcitrans and Thalassiosira pseudonana) and bacteria isolated from a diatom. Harmful Algae 58:45–50. doi:10.1016/j.toxicon.2015.11.011.
  • Richer, R., S. A. Banack, J. S. Metcalf, and P. A. Cox. 2015. The persistence of cyanobacterial toxins in desert soils. Journal of Arid Environments 112:134–39. doi:10.1016/j.jaridenv.2014.01.023.
  • Rodgers, K. J., and N. Shiozawa. 2008. Misincorporation of amino acid analogues into proteins by biosynthesis. The International Journal of Biochemistry & Cell Biology 40:1452–66. doi:10.1016/j.biocel.2008.01.009.
  • Rodgers-Johnson, P., R. M. Garruto, R. Yanagihara, K. M. Chen, D. C. Gajdusek, and C. J. GibbsJr. 1986. Amyotrophic lateral sclerosis and Parkinsonism-dementia on Guam: A 30-year evaluation of clinical and neuropathologic trends. Neurology 36:7–13. doi:10.1212/WNL.36.1.7.
  • Rogers, R. F. 1995. Destiny’s landfall: A history of Guam. Honolulu, HI: University of Hawaii Press.
  • Roman, G. C. 1996. Neuroepidemiology of amyotrophic lateral sclerosis: Clues to aetiology and pathogenesis. Journal of Neurology, Neurosurgery 61:131–37. doi:10.1136/jnnp.61.2.131.
  • Roney, B. R., R. H. Li, S. A. Banack, S. Murch, R. Honegger, and P. A. Cox. 2009. Consumption of fa cai Nostoc soup: A potential for BMAA exposure from Nostoc cyanobacteria in China? Amyotrophic Lateral Sclerosis 10:44–49. doi:10.3109/17482960903273031.
  • Rosen, J., and K. E. Hellenas. 2008. Determination of the neurotoxin BMAA (beta-N-methylamino-L-alanine) in cycad seed and cyanobacteria by LC-MS/MS (liquid chromatography tandem mass spectrometry). The Analyst 133:1785–89. doi:10.1039/b809231a.
  • Rosen, J., E. Westerberg, S. Schmiedt, and K. E. Hellenas. 2016. BMAA detected as neither free nor protein bound amino acid in blue mussels. Toxicon 109:45–50. doi:10.1016/j.toxicon.2015.11.008.
  • Safe, S. 1993. Toxicology, structure-function relationship, and human and environmental health impacts of polychlorinated biphenyls: progress and problems. Environmental Health Perspectives 100:259–68.
  • Schneider, S. A. 2016. Neurodegeneration with brain iron accumulation. Current Neurology and Neuroscience Reports 16:9. doi:10.1007/s11910-015-0608-3.
  • Scott, L. L., S. Downing, R. R. Phelan, and T. G. Downing. 2014. Environmental modulation of microcystin and beta-N-methylamino-L-alanine as a function of nitrogen availability. Toxicon 87:1–5. doi:10.1016/j.toxicon.2014.05.001.
  • Scott, P. M., B. Niedzwiadek, D. F. Rawn, and B. P. Lau. 2009. Liquid chromatographic determination of the cyanobacterial toxin beta-N-methylamino-L-alanine in algae food supplements, freshwater fish, and bottled water. Journal of Food Protection 72:1769–73. doi:10.4315/0362-028X-72.8.1769.
  • Seawright, A. A., A. W. Brown, C. C. Nolan, and J. B. Cavanagh. 1990. Selective degeneration of cerebellar cortical neurons caused by cycad neurotoxin, L-beta-methylaminoalanine (L-BMAA), in rats. Neuropathology and Applied Neurobiology 16:153–69. doi:10.1111/j.1365-2990.1990.tb00944.x.
  • Shankar, S. K., R. Yanagihara, R. M. Garruto, I. Grundke-Iqbal, K. S. Kosik, and D. C. Gajdusek. 1989. Immunocytochemical characterization of neurofibrillary tangles in amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam. Annals of Neurology 25:146–51. doi:10.1002/(ISSN)1531-8249.
  • Shen, W. B., K. A. McDowell, A. A. Siebert, S. M. Clark, N. V. Dugger, K. M. Valentino, H. A. Jinnah, C. Sztalryd, P. S. Fishman, C. A. Shaw, M. S. Jafri, and P. J. Yarowsky. 2010. Environmental neurotoxin-induced progressive model of Parkinsonism in rats. Annals of Neurology 68:70–80. doi:10.1002/ana.22018.
  • Shiraki, H. 1969. The neuropathology of Amyotrophic lateral sclerosis (ALS) in the Kii Peninsula and other areas of Japan. In Motor neuron diseases: Research on amyotrophic lateral sclerosis and related disorders, eds. F. H. NorrisJr, and L. T. Kurland, 80–84. New York, NY: Grune and Stratton.
  • Sieber, S. M., P. Correa, D. W. Dalgard, K. R. McIntire, and R. H. Adamson. 1980. Carcinogenicity and hepatotoxicity of cycasin and its aglycone methylazoxymethanol acetate in nonhuman primates. Journal of the National Cancer Institute 65:177–89.
  • Sieh, W., Y. Choi, N. H. Chapman, U. K. Craig, E. J. Steinbart, J. H. Rothstein, K. Oyanagi, R. M. Garruto, T. D. Bird, D. R. Galasko, G. D. Schellenberg, and E. M. Wijsman. 2009. Identification of novel susceptibility loci for Guam neurodegenerative disease: Challenges of genome scans in genetic isolates. Human Molecular Genetics 18:3725–38. doi:10.1093/hmg/ddp300.
  • Singh-Blom, A., R. A. Hughes, and A. D. Ellington. 2014. An amino acid depleted cell-free protein synthesis system for the incorporation of non-canonical amino acid analogs into proteins. Journal of Biotechnology 178:12–22. doi:10.1016/j.jbiotec.2014.02.009.
  • Smith, Q. R., H. Nagura, Y. Takada, and M. W. Duncan. 1992. Facilitated transport of the neurotoxin, beta-N-methylamino-L-alanine, across the blood-brain barrier. Journal of Neurochemistry 58:1330–37. doi:10.1111/j.1471-4159.1992.tb11346.x.
  • Snyder, L. R., R. Cruz-Aguado, M. Sadilek, D. Galasko, C. A. Shaw, and T. J. Montine. 2009. Lack of cerebral BMAA in human cerebral cortex. Neurology 72:1360–61. doi:10.1212/WNL.0b013e3181a0fed1.
  • Snyder, L. R., J. C. Hoggard, T. J. Montine, and R. E. Synovec. 2010. Development and application of a comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry method for analysis of L- β-methylamino-alanine in human tissue. Journal of Chromatography A 1217:4639–47. doi:10.1016/j.chroma.2010.04.065.
  • Soto, C. 2003. Unfolding the role of protein misfolding in neurodegenerative diseases. Nature Reviews. Neuroscience 4:49–60. doi:10.1038/nrn1007.
  • Spacil, Z., J. Eriksson, S. Jonasson, U. Rasmussen, L. L. Ilag, and B. Bergman. 2010. Analytical protocol for identification of BMAA and DAB in biological samples. The Analyst 135:127–32. doi:10.1039/B921048B.
  • Spatz, M., and G. L. Laqueur. 1967. Transplacental induction of tumors in Sprague-Dawley rats with crude cycad material. Journal of the National Cancer Institute 38:233–39.
  • Spencer, P. 1989. Western pacific ALS-Parkinsonism-dementia: A model of neuronal aging triggered by environmental toxins. In Parkinsonism and aging, ed. D. B. Calne, 133–44. New York, NY: Raven Press.
  • Spencer, P. S., R. G. Allen, G. E. Kisby, and A. C. Ludolph. 1990. Excitotoxic disorders. Science 248:144. doi:10.1126/science.2326627.
  • Spencer, P. S., C. E. Garner, V. S. Palmer, and G. E. Kisby. 2016. Vervets and macaques: Similarities and differences in their responses. Neurotoxicology 56:284–286. doi:10.1016/j.neuro.2016.03.018.
  • Spencer, P. S., G. E. Kisby, and A. C. Ludolph. 1991. Slow toxins, biologic markers, and long-latency neurodegenerative disease in the western Pacific region. Neurology Supplement 2 41:62–66.
  • Spencer, P. S., P. B. Nunn, J. Hugon, A. C. Ludolph, S. M. Ross, D. N. Roy, and R. C. Robertson. 1987c. Guam amyotrophic lateral sclerosis-Parkinsonism-dementia linked to a plant excitant neurotoxin. Science 237:517–22. doi:10.1126/science.3603037.
  • Spencer, P. S., M. Ohta, and V. S. Palmer. 1987a. Cycad use and motor neurone disease in Kii Peninsula of Japan. Lancet 2:1462–63. doi:10.1016/S0140-6736(87)91159-7.
  • Spencer, P. S., V. S. Palmer, A. Herman, and A. Asmedi. 1987b. Cycad use and motor neurone disease in Irian Jaya. Lancet 2:1273–74. doi:10.1016/S0140-6736(87)91883-6.
  • Spencer, P. S., V. S. Palmer, and A. C. Ludolph. 2005. On the decline and etiology of high-incidence motor system disease in West Papua (Southwest New Guinea). Movement Disorders 20 Supplement 12:S119–S126. doi:10.1002/mds.20552.
  • Stanhope, J. M., J. A. Brody, and C. E. Morris. 1972. Epidemiologic features of amyotropic lateral sclerosis and Parkinsonism-dementia in Guam, Mariana Islands. International Journal of Epidemiology 1:199–210. doi:10.1093/ije/1.3.199.
  • Staton, P. C., and D. R. Bristow. 1997. The dietary excitotoxins beta-N-methylamino-L-alanine and beta-N-oxalylamino-L-alanine induce necrotic- and apoptotic-like death of rat cerebellar granule cells. Journal of Neurochemistry 69:1508–18. doi:10.1046/j.1471-4159.1997.69041508.x.
  • Steahly, L. P., and C. A. Peterson. 1982. Ophthalmomyiasis. Annals of Ophthalmology 14:137–39.
  • Steele, J. C., J. C. Richardson, and J. Olszewski. 1964. Progressive Supranuclear Palsy. A heterogeneous degeneration involving the brain stem, basal ganglia and cerebellum with vertical gaze and pseudobulbar palsy, Nuchal dystonia and dementia. Archives of Neurology 10:333–59. doi:10.1001/archneur.1964.00460160003001.
  • Steele, J. C., R. Wresch, S. D. Hanlon, J. Keystone, and Y. Ben-Shlomo. 2015. A unique retinal epitheliopathy is associated with amyotrophic lateral sclerosis/Parkinsonism dementia complex of Guam. Movement Disorders 30:1271–75. doi:10.1002/mds.v30.9.
  • Stommel, E. W., N. C. Field, and T. A. Caller. 2013. Aerosolization of cyanobacteria as a risk factor for amyotrophic lateral sclerosis. Medical Hypotheses 80:142–45. doi:10.1016/j.mehy.2012.11.012.
  • Stone, B. C. 1970. The flora of Guam. Micronesica 6:1–659.
  • Sundar, P. D., C. E. Yu, W. Sieh, E. Steinbart, R. M. Garruto, K. Oyanagi, U. K. Craig, T. D. Bird, E. M. Wijsman, D. R. Galasko, and G. D. Schellenberg. 2007. Two sites in the MAPT region confer genetic risk for Guam ALS/PDC and dementia. Human Molecular Genetics 16:295–306. doi:10.1093/hmg/ddl463.
  • Surendranathan, A., J. B. Rowe, and J. T. O’Brien. 2015. Neuroinflammation in Lewy Body dementia. Parkinsonism & Related Disorders 21:1398–406. doi:10.1016/j.parkreldis.2015.10.009.
  • Tabata, R. C., J. M. Wilson, P. Ly, P. Zwiegers, D. Kwok, J. M. Van Kampen, N. Cashman, and C. A. Shaw. 2008. Chronic exposure to dietary sterol glucosides is neurotoxic to motor neurons and induces an ALS-PDC phenotype. Neuromolecular Medicine 10:24–39. doi:10.1007/s12017-007-8020-z.
  • Torbick, N., S. Hession, E. Stommel, and T. Caller. 2014. Mapping Amyotrophic lateral sclerosis lake risk factors across northern New England. International Journal of Health Geographics 13:1. doi:10.1186/1476-072X-13-1.
  • Torres, J., L. L. Iriarte, and L. T. Kurlund. 1957. Amyotrophic lateral sclerosis in Guamanian in Californians. California Medicine 86:385–88.
  • Troost, B. T., and R. B. Daroff. 1977. Ocular motor defects in progressive Supranuclear Palsy. Annals of Neurology 2:397–403. doi:10.1002/ana.410020509.
  • Umahara, T., A. Hirano, S. Kato, N. Shibata, and S. H. Yen. 1994. Demonstration of neurofibrillary tangles and neuropil thread-like structures in spinal cord white matter in Parkinsonism dementia complex on Guam and in Guamanian amyotrophic lateral sclerosis. Acta Neuropathologica 88:180–84. doi:10.1007/BF00294512.
  • Van Onselen, R., N. A. Cook, R. R. Phelan, and T. G. Downing. 2015. Bacteria do not incorporate beta-N-methylamino-L-alanine into their proteins. Toxicon 102:55–61. doi:10.1016/j.toxicon.2015.05.014.
  • Vega, A., and E. A. Bell. 1967. α-Amino-β-methylaminopropionic acid, a new amino acid from seeds of Cycas circinalis. Phytochemistry 6:759–62. doi:10.1016/S0031-9422(00)86018-5.
  • Vega, A., E. A. Bell, and P. B. Nunn. 1968. The preparation of L- and D-alpha-aminobeta-methylaminopropionic acids and the identification of the compound isolated from Cycas circinalis as the L-isomer. Phytochemistry 7:1885–87. doi:10.1016/S0031-9422(00)86667-4.
  • Walton, J. R. 2006. Aluminum in hippocampal neurons from humans with Alzheimer’s disease. Neurotoxicology 27:385–94. doi:10.1016/j.neuro.2005.11.007.
  • Walton, J. R. 2010. Evidence for participation of aluminum in neurofibrillary tangle formation and growth in Alzheimer’s disease. Journal of Alzheimer’s Disease 22:65–72.
  • Whiting, M. G. 1963. Toxicity of cycads. Economic Botany 17:271–302. doi:10.1007/BF02860136.
  • Whiting, M. G. 1964. Food practices in Als Foci in Japan, the Marianas, and New Guinea. Federation Proceedings 23:1343–45.
  • WHO. 2011. Guidelines for drinking-water quality. 4th edn. Chapter 12: Chemical fact sheet. 386–87. Geneva: WHO.
  • Wiles, G. J. 1987a. Current research and future management of marianas fruit bats (Chiroptera pteropodidae) on Guam. Australian Mammol 10:93–95.
  • Wiles, G. J. 1987b. The status of fruits on Guam. Pacific Science 41:148–57.
  • Williams, M., G. D. Todd, N. Roney, J. Crawford, C. Coles, P. R. McClure, J. D. Garey, K. Zaccaria, and M. Citra. 2012. Toxicological profile for manganese. Atlanta, GA: U.S. Department of Health and Human Services, Agency for Toxic Substances and Disease Registry.
  • Wilson, J. M., I. Khabazian, M. C. Wong, A. Seyedalikhani, J. S. Bains, B. A. Pasqualotto, D. E. Williams, R. J. Andersen, R. J. Simpson, R. Smith, U. K. Craig, L. T. Kurland, and C. A. Shaw. 2002. Behavioral and neurological correlates of ALS-Parkinsonism dementia complex in adult mice fed washed cycad flour. Neuromolecular Medicine 1:207–21. doi:10.1385/NMM:1:3:207.
  • Xie, X., M. Basile, and D. C. Mash. 2013. Cerebral uptake and protein incorporation of cyanobacterial toxin beta-N-methylamino-L-alanine. Neuroreport 24:779–84. doi:10.1097/WNR.0b013e328363fd89.
  • Yanagihara, R., R. M. Garruto, D. C. Gajdusek, A. Tomita, T. Uchikawa, Y. Konagaya, C. Km, I. Sobue, P. Cc, and C. J. GibbsJr . 1984. Calcium and vitamin D metabolism in Guamanian Chamorros with amyotrophic lateral sclerosis and Parkinsonism-dementia. Annals of Neurology 15:42–48. doi:10.1002/ana.410150108.
  • Yase, Y. 1970. Neurologic disease in the western Pacific islands, with a report on the focus of amyotrophic lateral sclerosis found in the Kii peninsula, Japan. The American Journal of Tropical Medicine and Hygiene 19: 155–66.
  • Yase, Y. 1972. The pathogenesis of amyotrophic lateral sclerosis. Lancet 2:292–96. doi:10.1016/S0140-6736(72)92903-0.
  • Yase, Y. 1978. [Motor neuron disease]. Nihon Rinsho 35 (Suppl):1716–17.
  • Yase, Y. 1979. ALS in the Kii Peninsula: One possible etiological hypothesis. In Amyotrophic lateral sclerosis, eds. T. Tsubaki, and Y. Toyokwa, 307–18. Tokyo: University of Tokyo Press.
  • Yasui, M., K. Ota, and M. Yoshida. 1997. Effects of low calcium and magnesium dietary intake on the central nervous system tissues of rats and calcium-magnesium related disorders in the Amyotrophic lateral sclerosis focus in the Kii Peninsula of Japan. Magnesium Research 10:39–50.
  • Yasui, M., Y. Yase, T. Kihira, K. Adachi, and Y. Suzuki. 1992. Magnesium and calcium contents in CNS tissues of amyotrophic lateral sclerosis patients from the Kii peninsula, Japan. European Neurology 32:95–98. doi:10.1159/000116800.
  • Yasui, M., Y. Yase, and K. Ota. 1991a. Distribution of calcium in central nervous system tissues and bones of rats maintained on calcium-deficient diets. Journal of the Neurological Sciences 105:206–10. doi:10.1016/0022-510X(91)90146-X.
  • Yasui, M., Y. Yase, K. Ota, M. Mukoyama, and K. Adachi. 1991b. High aluminum deposition in the central nervous system of patients with amyotrophic lateral sclerosis from the Kii Peninsula, Japan: Two case reports. Neurotoxicology 12:277–83.
  • Yoshimasu, F., Y. Uebayashi, Y. Yase, S. Iwata, and K. Sasajima. 1976. Studies on amyotrophic lateral sclerosis by neutron activation analysis. Folia Psychiatrica et Neurologica Japonica 30:49–55.
  • Yoshimasu, F., M. Yasui, Y. Yase, S. Iwata, D. C. Gajdusek, C. J. GibbsJr., and K. Chen. 1980. Studies on amyotrophic lateral sclerosis by neutron activation analysis–2. Comparative study of analytical results on Guam PD, Japanese ALS and Alzheimer disease cases. Folia Psychiatrica et Neurologica Japonica 34:75–82.
  • Yoshimasu, F., M. Yasui, Y. Yase, Y. Uebayashi, S. Tanaka, S. Iwata, K. Sasajima, D. C. Gajdusek, C. J. Gibbs, and K. Chen. 1982. Studies on amyotrophic lateral sclerosis by neutron activation analysis. 3. Systematic analysis of metals on Guamanian ALS and PD cases. Folia Psychiatrica et Neurologica Japonica 36:173–79.
  • Zhang, Z. X., D. W. Anderson, and N. Mantel. 1990. Geographic patterns of Parkinsonism-dementia complex on Guam. 1956 through 1985. Archives of Neurology 47:1069–74. doi:10.1001/archneur.1990.00530100031010.
  • Zhang, Z. X., D. W. Anderson, N. Mantel, and G. C. Roman. 1996. Motor neuron disease on Guam: Geographic and familial occurrence, 1956-85. Acta Neurologica Scandinavica 94:51–59. doi:10.1111/j.1600-0404.1996.tb00039.x.
  • Zolan, W. J., and L. Ellis-Neill. 1986. Concentrations of aluminum, magnesium, iron, and calcium in four southern Guam rivers. Technical Report No. 64: 1–68. Guam: University of Guam; Water and Energy Institute of the Western Pacific.
  • Zurawell, R. W., H. Chen, J. M. Burke, and E. E. Prepas. 2005. Hepatotoxic cyanobacteria: A review of the biological importance of microcystins in freshwater environments. Journal Toxicogical Environment Health B 8:1–37. doi:10.1080/10937400590889412.

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