Advanced search
Publication Cover
Expert Opinion on Emerging Drugs Volume 13, 2008 - Issue 2
Submit an article Journal homepage
205
Views
23
CrossRef citations to date
0
Altmetric
Review

Emerging amyloid beta (Ab) peptide modulators for the treatment of Alzheimer's disease (AD)

Walter J Lukiw Associate Professor of Neuroscience and Ophthalmology Louisiana State University Health Sciences Center, LSU Neuroscience Center of Excellence, 2020 Gravier Street, Suite 8B8, New Orleans, LA 70112-2272, USA +1 504 599 0842; +1 504 568 5801; [email protected]
, MS PhD
Pages 255-271 | Published online: 08 Jun 2008

Bibliography

  • Thompson PM, Hayashi KM, Dutton RA, et al. Tracking Alzheimer's disease. Ann NY Acad Sci 2007;1097:183-214
  • Reddy PH. Amyloid precursor protein-mediated free radicals and oxidative damage: implications for the development and progression of Alzheimer's disease. J Neurochem 2006;96:1-13
  • Zhao Y, Cui JG, Lukiw WJ. Natural secretory products of human neural and microvessel endothelial cells: implications in pathogenic “spreading” and Alzheimer's disease. Mol Neurobiol 2006;34:181-92
  • Loh KP, Huang SH, De Silva R, et al. Oxidative stress: apoptosis in neuronal injury. Curr Alzheimer Res 2006;3:327-37
  • Armstrong RA. Plaques and tangles and the pathogenesis of Alzheimer's disease. Folia Neuropathol 2006;44:1-11
  • Hardy J. Alzheimer's disease: the amyloid cascade hypothesis: an update and reappraisal. J Alzheimers Dis 2006;9:151-3
  • Golde TE, Dickson D, Hutton M. Filling the gaps in the Aβ cascade hypothesis of Alzheimer's disease. Curr Alzheimer Res 2006;3:421-30
  • Esiri MM, Chance SA. Vulnerability to Alzheimer's pathology in neocortex: the roles of plasticity and columnar organization. J Alzheimers Dis 2006;9:79-89
  • Cui JG, Hill JM, Zhao Y, Lukiw WJ. Expression of inflammatory genes in the primary visual cortex of late-stage Alzheimer's disease. Neuroreport 2007;18:115-9
  • van de Pol LA, Korf ES, van der Flier WM, et al. Magnetic resonance imaging predictors of cognition in mild cognitive impairment. Arch Neurol 2007;64:1023-8
  • Marshall GA, Monserratt L, Harwood D, et al. Positron emission tomography metabolic correlates of apathy in Alzheimer disease. Arch Neurol 2007;64:1015-20
  • Velliquette RA, O'Connor T, Vassar R. Energy inhibition elevates beta-secretase levels and activity and is potentially amyloidogenic in APP transgenic mice: possible early events in Alzheimer's disease pathogenesis. J Neurosci 2005;25:10874-83
  • Mott RT, Hulette CM. Neuropathology of Alzheimer's disease. Neuroimaging Clin N Am 2005;15:755-65
  • Siemers ER, Quinn JF, Kaye J, et al. Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease. Neurology 2006;66:602-4
  • Tomita T. At the frontline of Alzheimer's disease treatment: gamma-secretase inhibitor/modulator mechanism. Naunyn Schmiedebergs Arch Pharmacol 2007; [Epub ahead of print]. Available from: http://www.medicalnewstoday.com/articles/43113.php
  • Siemers ER, Dean RA, Friedrich S, et al. Safety, tolerability, and effects on plasma and cerebrospinal fluid amyloid-beta after inhibition of gamma-secretase. Clin Neuropharmacol 2007;30:317-25
  • Imbimbo BP. Therapeutic potential of gamma-secretase inhibitors and modulators. Curr Top Med Chem 2008;8:54-61
  • Van Broeck B, Van Broeckhoven C, Kumar-Singh S. Current insights into molecular mechanisms of Alzheimer disease and their implications for therapeutic approaches. Neurodegener Dis 2007;4:349-65
  • Dong J, Lu K, Lakdawala A, et al. Controlling amyloid growth in multiple dimensions. Amyloid 2006;13:206-15
  • Selkoe D, Kopan R. Notch and presenilin: regulated intramembrane proteolysis links development and degeneration. Ann Rev Neurosci 2003;26:565-97
  • Turner PR, Bourne K, Garama D, et al. Production, purification and functional validation of human secreted amyloid precursor proteins for use as neuropharmacological reagents. J Neurosci Methods 2007;164:68-74
  • Lukiw WJ, Bazan NG. Survival signaling in Alzheimer's disease. Biochem Soc Trans 2006;34:1277-82
  • Thornton E, Vink R, Blumbergs PC, Van Den Heuvel C. Soluble amyloid precursor protein alpha reduces neuronal injury and improves functional outcome following diffuse traumatic brain injury in rats. Brain Res 2006;1094:38-46
  • Bohm C, Seibel NM, Henkel B, et al. SorLA signaling by regulated intramembrane proteolysis. J Biol Chem 2006;281:14547-53
  • Offe K, Dodson SE, Shoemaker JT, et al. The lipoprotein receptor LR11 regulates amyloid beta production and amyloid precursor protein traffic in endosomal compartments. J Neurosci 2006;26:1596-603
  • Available from: www.myriad.com/alzheimers/sala-animation.php
  • Rogaeva E, Meng Y, Lee JH, et al. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet 2007;39:168-77
  • Zhao Y, Cui JG, Lukiw WJ. Reduction of sortilin-1 in Alzheimer hippocampus and in cytokine-stressed human brain cells. Neuroreport 2007;18:1187-91
  • Lukiw WJ, Pappolla M, Pelaez RP, Bazan NG. Alzheimer's disease – a dysfunction in cholesterol and lipid metabolism. Cell Mol Neurobiol 2005;25:475-83
  • Vagnucci AH, Li WW. Alzheimer's disease and angiogenesis. Lancet 2003;361:605-8
  • Thal LJ. Prevention of Alzheimer disease. Alzheimer Dis Assoc Disord 2006;20:S97-9
  • Hardy J. A hundred years of Alzheimer's disease research. Neuron 2006;52:3-13
  • Iqbal K, Grundke-Iqbal I. Discoveries of tau, abnormally hyperphosphorylated tau and others of neurofibrillary degeneration: a personal historical perspective. J Alzheimers Dis 2006;9:219-42
  • Infante-Duarte C, Waiczies S, Wuerfel J, Zipp F. New developments in understanding and treating neuroinflammation. J Mol Med 2008; [Epub ahead of print]
  • Tanzi RE, Bertram L. Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell 2005;120:545-55
  • Lukiw WJ. 100 years of Alzheimer's disease research: are we any closer to a cure? Aging Health 2007;3:279-82
  • Maslow K, and The Alzheimer's Association. 2008 Alzheimer's disease facts and figures. Alzheimer's & Dementia 2008;4:110-33
  • Zhu CW, Scarmeas N, Torgan R, et al. Longitudinal study of effects of patient characteristics on direct costs in Alzheimer disease. Neurology 2006;67:998-1005
  • Lyketsos CG, Colenda CC, Beck C, et al. Task Force of American Association for Geriatric Psychiatry. Position statement of the American Association for Geriatric Psychiatry regarding principles of care for patients with dementia resulting from Alzheimer disease. Am J Geriatr Psychiatry 2006;14:561-72
  • Doody RS. Current treatments for Alzheimer's disease: cholinesterase inhibitors. J Clin Psychiatry 2003;64(Suppl 9):11-7
  • Seltzer B. Donepezil: an update. Expert Opin Pharmacother 2007;8:1011-23
  • Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev 2006;1:CD00593
  • Blennow K, de Leon MJ, Zetterberg H. Alzheimer's disease. Lancet 2006;368:387-403
  • Holzgrabe U, Kapkova P, Alptuzun V, et al. Targeting acetylcholin-esterase to treat neurodegeneration. Expert Opin Ther Targets 2007;11:161-79
  • Mayor S. Regulatory authorities review use of galantamine in mild cognitive impairment. BMJ 2005;330:276
  • Kaduszkiewicz H, Zimmermann T, Beck-Bornholdt HP, van den Bussche H. Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials. BMJ 2005;331:321-7
  • Tanovice A, Alfaro V. Glutamate-related excitotoxicity neuroprotection with memantine, an uncompetitive antagonist of NMDA-glutamate receptor, in Alzheimer's disease and vascular dementia. Rev Neurol 2006;42:607-16
  • Areosa SA, Sherriff F, McShane R. Memantine for dementia. Cochrane Database Syst Rev 2005;3:CD003154
  • van Dyck CH, Tariot PN, Meyers B, Malca Resnick E; Memantine MEM-MD-01 Study Group. A 24-week randomized, controlled trial of memantine in patients with moderate-to-severe Alzheimer disease. Alzheimer Dis Assoc Disord 2007;21:136-43
  • Creeley CE, Wozniak DF, Nardi A, et al. Donepezil markedly potentiates memantine neurotoxicity in the adult rat brain. Neurobiol Aging 2008;29:153-67
  • Mount C, Downton C. Alzheimer's disease: progress or profit? Nat Med 2006;3:1280-4
  • Iliffe S. The National Institute for Health and Clinical Excellence (NICE) and drug treatment for Alzheimer's disease. CNS Drugs 2007;21:177-84
  • Schenk D, Barbour R, Dunn W, et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999;400:173-7
  • McLaurin J, Cecal R, Kierstead ME, et al. Therapeutically effective antibodies against amyloid-beta peptide target amyloid-beta residues 4-10 and inhibit cytotoxicity and fibrillogenesis. Nat Med 2002;8:1263-9
  • Selkoe DJ, Schenk D. Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Ann Rev Pharmacol Toxicol 2003;43:545-84
  • Lichtlen P, Mohajeri MH. Antibody-based approaches in Alzheimer's research: safety, pharmacokinetics, metabolism, and analytical tools. J Neurochem 2008;104:859-74
  • Available from: http://www.athenagen.com/index.php?/athenagen/press_releases/48
  • CoMentis receives FDA clearance to begin human clinical trials for its disease-modifying Alzheimer's therapy. CoMentis News Room. Available from: www.athenagen.com/index.php?/athenagen/press_releases/45/ [Last accessed 11 April 2008]
  • Edwards JE, Moore RA. Statins in hypercholesterolaemia: a dose-specific meta-analysis of lipid changes in randomised, double blind trials. BMC Fam Pract 2003;4:18
  • Miller LJ, Chacko R. The role of cholesterol and statins in Alzheimer's disease. Ann Pharmacother 2004;38:91-8
  • Gelosa P, Cimino M, Pignieri A, et al. The role of HMG-CoA reductase inhibition in endothelial dysfunction and inflammation. Vasc Health Risk Manag 2007;3:567-77
  • Jasińska M, Owczarek J, Orszulak-Michalak D. Statins: a new insight into their mechanisms of action and consequent pleiotropic effects. Pharmacol Rep 2007;59:483-99
  • Parsons RB, Farrant JK, Price GC, et al. Regulation of the lipidation of beta-secretase by statins. Biochem Soc Trans 2007;35:577-82
  • Parvathy S, Ehrlich M, Pedrini S, et al. Atorvastatin-induced activation of Alzheimer's alpha secretase is resistant to standard inhibitors of protein phosphorylation-regulated ectodomain shedding. J Neurochem 2004;90:1005-10
  • Cordy JM, Hooper NM, Turner AJ. The involvement of lipid rafts in Alzheimer's disease. Mol Membr Biol 2006;23:111-22
  • Pappolla MA, Bryant-Thomas TK, Herbert D, et al. Hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology. Neurology 2003;61:199-205
  • Petanceska SS, DeRosa S, Sharma A, et al. Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol. J Mol Neurosci 2003;20:395-406
  • Wolozin B, Wang SW, Li NC, et al. Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. BMC Med 2007;5:20
  • Miyazaki A, Kanome T, Watanabe T. Inhibitors of acyl-coenzyme A: cholesterol acyltrans-ferase. Curr Drug Targets Cardiovasc Haematol Disord 2005;5:463-9
  • Brown WJ, Schmidt JA. Use of acyltransferase inhibitors to block vesicular traffic between the ER and Golgi complex. Methods Enzymol 2005;404:115-25
  • Burnett JR, Telford DE, Barrett PH, Huff MW. The ACAT inhibitor avasimibe increases the fractional clearance rate of postprandial triglyceride-rich lipoproteins in miniature pigs. Biochim Biophys Acta 2005;1738:10-8
  • Yatskar L, Fisher EA, Schwartzbard A. Ezetimibe: rationale and role in the management of hypercholesterolemia. Clin Cardiol 2006;29:52-5
  • Davignon J, Leiter LA. Ongoing clinical trials of the pleiotropic effects of statins. Vasc Health Risk Manag 2005;1:29-40
  • Arvanitakis Z, Schneider JA, Wilson RS, et al. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology 2008; Epub ahead of print]
  • Chaki O. Next generation selective estrogen receptor modulators. Clin Calcium 2006;16:145-52
  • Rodenburg J, Vissers MN, Daniels SR, et al. Lipid-lowering medications. Pediatr Endocrinol Rev 2004;2:171-80
  • Denke MA. Diet, lifestyle, and nonstatin trials: review of time to benefit. Am J Cardiol 2005;96:3-10
  • Townsend KP, Pratico D. Novel therapeutic opportunities for Alzheimer's disease: focus on nonsteroidal anti-inflammatory drugs. FASEB J 2005;19:1592-601
  • Huttunen HJ, Greco C, Kovacs DM. Knockdown of ACAT-1 reduces amyloidogenic processing of APP. FEBS Lett 2007;581:1688-92
  • Wright TM. Tramiprosate. Drugs Today 2006;42:291-8
  • Available from: http://seniorjournal.com/NEWS/Alzheimers/5-07-05Alzhemed.htm
  • Tramiprosate (ALZHEMED™) North American Phase III clinical trial progress update. Medical News Today. Available from: www.medicalnewstoday.com/articles/75040.php [Last accessed 11 April 2008]
  • Gasparini L, Ongini E, Wilcock D, Morgan D. Activity of flurbiprofen and chemically related anti-inflammatory drugs in models of Alzheimer's disease. Brain Res Brain Res Rev 2005;48:400-8
  • Available from: http://www.myriad.com/alzheimers/flurizan.php
  • Mazza M, Capuano A, Bria P, Mazza S. Ginkgo biloba and donepezil: a comparison in the treatment of Alzheimer's dementia in a randomized placebo-controlled double-blind study. Eur J Neurol 2006;13:981-5
  • Itil TM, Eralp E, Ahmed I, et al. The pharmacological effects of ginkgo biloba, a plant extract, on the brain of dementia patients in comparison with tacrine. Psychopharmacol Bull 1998;34:391-7
  • Chen F, Eckman EA, Eckman CB. Reductions in levels of the Alzheimer's amyloid beta peptide after oral administration of ginsenosides. FASEB J 2006;20:1269-71
  • Cheng Y, Shen LH, Zhang JT. Anti-amnestic and anti-aging effects of ginsenoside Rg1 and Rb1 and its mechanism of action. Acta Pharmacol Sin 2005;26:143-9
  • Fujiwara H, Iwasaki K, Furukawa K, et al. Uncaria rhynchophylla, a Chinese medicinal herb, has potent anti-aggregation effects on Alzheimer's beta-amyloid proteins. J Neurosci Res 2006;84:427-33
  • Eubanks LM, Rogers CJ, Beuscher AE, et al. A molecular link between the active component of marijuana and Alzheimer's disease pathology. Mol Pharm 2006;3:773-7
  • Dos Santos-Neto LL, de Vilhena Toledo MA, Medeiros-Souza P, de Souza GA. The use of herbal medicine in Alzheimer's disease: a systematic review. Evid Based Complement Altern Med 2006;3:441-5
  • Cuajungco MP, Frederickson CJ, Bush AI. Amyloid-beta metal interaction and metal chelation. Subcell Biochem 2005;38:235-54
  • Gaeta A, Hider RC. The crucial role of metal ions in neurodegeneration: the basis for a promising therapeutic strategy. Br J Pharmacol 2006;146:1041-59
  • Domingo JL. Aluminum and other metals in Alzheimer's disease: a review of potential therapy with chelating agents. J Alzheimers Dis 2006;10:331-41
  • Kruck TP, Cui JG, Percy ME, Lukiw WJ. Molecular shuttle chelation: the use of ascorbate, desferrioxamine and Feralex-G in combination to remove nuclear bound aluminum. Cell Mol Neurobiol 2004;24:443-59
  • Exley C. Aluminium and iron, but neither copper nor zinc, are key to the precipitation of beta-sheets of Abeta42 in senile plaque cores in Alzheimer's disease. J Alzheimers Dis 2006;10:173-7
  • Kruck TP, Percy ME, Lukiw WJ. Metal sulfate-mediated induction of pathogenic genes and repression by phenyl butyl nitrone and Feralex-G. Neuroreport 2008;19:245-9
  • Mukherjee PK, Chawla A, Loayza MS, Bazan NG. Docosanoids are multifunctional regulators of neural cell integrity and fate: significance in aging and disease. Prostaglandins Leukot Essent Fatty Acids 2007;77:233-8
  • Cole GM, Frautschy SA. Docosahexaenoic acid protects from amyloid and dendritic pathology in an Alzheimer's disease mouse model. Nutr Health 2006;18:249-59
  • Lukiw WJ, Cui JG, Marcheselli VL, et al. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest 2005;115:2774-83
  • Lukiw WJ. Cholesterol and 24S-hydroxycholesterol trafficking in Alzheimer's disease. Expert Rev Neurother 2006;6:683-93
  • Simons M, Keller P, De Strooper B, et al. Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc Natl Acad Sci USA 1998;95:6460-4
  • Spencer B, Rockenstein E, Crews L, et al. Novel strategies for Alzheimer's disease treatment. Expert Opin Biol Ther 2007;7:1853-67
  • Clare L, Wooks R, Moniz Cook E, et al. Cognitive rehabilitation and cognitive training for early-stage Alzheimer's disease and vascular dementia. Cochrane Database Syst Rev 2003;4:CD003260
  • Burgener SC, Buettner L, Coen Buckwalter K, et al. Evidence supporting nutritional interventions for persons in early stage Alzheimer's disease (AD). J Nutr Health Aging 2008;12:18-21
  • Burns A, O'Brien J; BAP Dementia Consensus Group; Auriacombe S, Ballard C, Broich K, et al. British Association for Psychopharmacology. Clinical practice with anti-dementia drugs: a consensus statement from British Association for Psychopharmacology. J Psychopharmacol 2006;20:732-55
  • Sparks DL, Connor DJ, Sabbagh MN, et al. Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: results of the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trial. Acta Neurol Scand Suppl 2006;185:3-7
  • Available from: http://www.alzforum.org/drg/drc/default.asp
  • Park IH, Hwang EM, Hong HS, et al. Lovastatin enhances Abeta production and senile plaque deposition in female Tg2576 mice. Neurobiol Aging 2003;24:637-43
  • Hoglund K, Wiklund O, Vanderstichel H, et al. Plasma levels of beta-amyloid(1-40), beta-amyloid(1-42), and total beta-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins. Arch Neurol 2004;61:333-7
  • Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian solid gold. Adv Exp Med Biol 2007;595:1-75
  • Ren Y, Houghton P, Hider RC. Relevant activities of extracts and constituents of animals used in traditional Chinese medicine for central nervous system effects associated with Alzheimer's disease. J Pharm Pharmacol 2006;58:989-96
  • Doraiswamy PM, Xiong GL. Pharmacological strategies for the prevention of Alzheimer's disease. Expert Opin Pharmacother 2006;7:1-10
  • Kumar V. Potential medicinal plants for CNS disorders: an overview. Phytother Res 2006;20:1023-35
  • Steele M, Stuchbury G, Munch G. The molecular basis of the prevention of Alzheimer's disease through healthy nutrition. Exp Gerontol 2007;42:28-36
  • Adams M, Gmünder F, Hamburger M. Plants traditionally used in age-related brain disorders: a survey of the ethnobotanical literature. J Ethnopharmacol 2007;113:363-81
  • Potterat O, Hamburger M. Drug discovery and development with plant-derived compounds. Prog Drug Res 2008;65:47-118

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.