The use of cerebrospinal fluid biomarkers to measure change in neurodegeneration in Alzheimer’s disease clinical trials

References

• Blennow K, De Leon MJ, Zetterberg H. Alzheimer’s disease. Lancet. 2006;368:387–403. ​​​
   PubMed Web of Science ®Google Scholar
• Seshadri S, Wolf PA. Lifetime risk of stroke and dementia: current concepts, and estimates from the Framingham study. Lancet Neurol. 2007;6:1106–1114.
   PubMed Web of Science ®Google Scholar
• Hebert LE, Weuve J, Scherr PA, et al. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology. 2013;80:1778–1783.
   PubMed Web of Science ®Google Scholar
• Olsson B, Zetterberg H, Hampel H, et al. Biomarker-based dissection of neurodegenerative diseases. Prog Neurobiol. 2011;95:520–534.
   PubMed Web of Science ®Google Scholar
• Alzheimer A. Über eine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiat. 1907;64:146–148.
   Google Scholar
• Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science. 1992;256:184–185.
   PubMed Web of Science ®Google Scholar
• Olsson B, Lautner R, Andreasson U, et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15:673–684.
   PubMed Web of Science ®Google Scholar
• Wallin AK, Blennow K, Zetterberg H, et al. CSF biomarkers predict a more malignant outcome in Alzheimer disease. Neurology. 2010;74:1531–1537.
   PubMed Web of Science ®Google Scholar
• Riemenschneider M, Wagenpfeil S, Vanderstichele H, et al. Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias. Mol Psychiatry. 2003;8:343–347.
   PubMed Web of Science ®Google Scholar
• Hesse C, Rosengren L, Andreasen N, et al. Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke. Neurosci Lett. 2001;297:187–190.
   PubMed Web of Science ®Google Scholar
• Grundke-Iqbal I, Iqbal K, Tung YC, et al. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A. 1986;83:4913–4917.
   PubMed Web of Science ®Google Scholar
• Buerger K, Ewers M, Pirttila T, et al. CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer’s disease. Brain. 2006;129:3035–3041.
   PubMed Web of Science ®Google Scholar
• Blom ES, Giedraitis V, Zetterberg H, et al. Rapid progression from mild cognitive impairment to Alzheimer’s disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype. Dement Geriatr Cogn Disord. 2009;27:458–464.
   PubMed Web of Science ®Google Scholar
• Samgard K, Zetterberg H, Blennow K, et al. Cerebrospinal fluid total tau as a marker of Alzheimer’s disease intensity. Int J Geriatr Psychiatry. 2010;25:403–410.
   PubMed Web of Science ®Google Scholar
• Glenner GG, Wong CW Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984;120:885–890.
   Google Scholar
• Kang J, Lemaire HG, Unterbeck A, et al. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature. 1987;325:733–736.
   PubMed Web of Science ®Google Scholar
• Goate A, Chartier-Harlin MC, Mullan M, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature. 1991;349:704–706.
   PubMed Web of Science ®Google Scholar
• Alzheimer's Disease Collaborative Group. The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. Nat Genet. 1995;11:219–222. ​​​
   PubMed Web of Science ®Google Scholar
• Levy-Lahad E, Wasco W, Poorkaj P, et al. Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science. 1995;269:973–977.
   PubMed Web of Science ®Google Scholar
• Jervis GA. Early senile dementia in mongoloid idiocy. Am J Psychiatry. 1948;105:102–106.
   PubMed Web of Science ®Google Scholar
• Blennow K, Mattsson N, Scholl M, et al. Amyloid biomarkers in Alzheimer’s disease. Trends Pharmacol Sci. 2015;36:297–309.
   PubMed Web of Science ®Google Scholar
• McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–269.
   PubMed Web of Science ®Google Scholar
• Hansson O, Zetterberg H, Buchhave P, et al. Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006;5:228–234.
   PubMed Web of Science ®Google Scholar
• Wiltfang J, Esselmann H, Bibl M, et al. Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-Tau in patients with low- and high-CSF A beta 40 load. J Neurochem. 2007;101:1053–1059.
   PubMed Web of Science ®Google Scholar
• Zetterberg H. Neurofilament light: a dynamic cross-disease fluid biomarker for neurodegeneration. Neuron. 2016;91:1–3.
   PubMed Web of Science ®Google Scholar
• Zetterberg H, Skillback T, Mattsson N, et al. Association of cerebrospinal fluid neurofilament light concentration with Alzheimer disease progression. JAMA Neurol. 2016;73:60–67.
   PubMed Web of Science ®Google Scholar
• de Jong D, Jansen RW, Pijnenburg YA, et al. CSF neurofilament proteins in the differential diagnosis of dementia. J Neurol Neurosurg Psychiatry. 2007;78:936–938.
   PubMed Web of Science ®Google Scholar
• Landqvist Waldo M, Frizell Santillo A, Passant U, et al. Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia. BMC Neurol. 2013;13:54.
   PubMed Web of Science ®Google Scholar
• Sjogren M, Rosengren L, Minthon L, et al. Cytoskeleton proteins in CSF distinguish frontotemporal dementia from AD. Neurology. 2000;54:1960–1964.
   PubMed Web of Science ®Google Scholar
• Skillback T, Farahmand B, Bartlett JW, et al. CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival. Neurology. 2014;83:1945–1953.
   PubMed Web of Science ®Google Scholar
• Hall S, Ohrfelt A, Constantinescu R, et al. Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders. Arch Neurol. 2012;69:1445–1452.
   PubMed Web of Science ®Google Scholar
• Magdalinou NK, Paterson RW, Schott JM, et al. A panel of nine cerebrospinal fluid biomarkers may identify patients with atypical parkinsonian syndromes. J Neurol Neurosurg Psychiatry. 2015;86:1240–1247.
   PubMed Web of Science ®Google Scholar
• Weydt P, Oeckl P, Huss A, et al. Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis. Ann Neurol. 2016;79:152–158.
   PubMed Web of Science ®Google Scholar
• van Eijk JJ, van Everbroeck B, Abdo WF, et al. CSF neurofilament proteins levels are elevated in sporadic Creutzfeldt-Jakob disease. J Alzheimers Dis. 2010;21:569–576.
   PubMed Web of Science ®Google Scholar
• Steinacker P, Blennow K, Halbgebauer S, et al. Neurofilaments in blood and CSF for diagnosis and prediction of onset in Creutzfeldt-Jakob disease. Sci Rep. 2016;6:38737.
   PubMed Web of Science ®Google Scholar
• Thorsell A, Bjerke M, Gobom J, et al. Neurogranin in cerebrospinal fluid as a marker of synaptic degeneration in Alzheimer’s disease. Brain Res. 2010;1362:13–22.
   PubMed Web of Science ®Google Scholar
• Kvartsberg H, Duits FH, Ingelsson M, et al. Cerebrospinal fluid levels of the synaptic protein neurogranin correlates with cognitive decline in prodromal Alzheimer’s disease. Alzheimers Dement. 2015;11:1180–1190.
   PubMed Web of Science ®Google Scholar
• Kvartsberg H, Portelius E, Andreasson U, et al. Characterization of the postsynaptic protein neurogranin in paired cerebrospinal fluid and plasma samples from Alzheimer’s disease patients and healthy controls. Alzheimers Res Ther. 2015;7:40.
   PubMed Web of Science ®Google Scholar
• Hellwig K, Kvartsberg H, Portelius E, et al. Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer’s disease. Alzheimers Res Ther. 2015;7:74.
   PubMed Web of Science ®Google Scholar
• Kester MI, Teunissen CE, Crimmins DL, et al. Neurogranin as a cerebrospinal fluid biomarker for synaptic loss in symptomatic Alzheimer disease. JAMA Neurol. 2015;72:1275–1280.
   PubMed Web of Science ®Google Scholar
• Wellington H, Paterson RW, Portelius E, et al. Increased CSF neurogranin concentration is specific to Alzheimer disease. Neurology. 2016;86:829–835.
   PubMed Web of Science ®Google Scholar
• Portelius E, Zetterberg H, Skillback T, et al. Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer’s disease. Brain. 2015;138:3373–3385.
   PubMed Web of Science ®Google Scholar
• Tarawneh R, D’Angelo G, Crimmins D, et al. Diagnostic and prognostic utility of the synaptic marker neurogranin in Alzheimer disease. JAMA Neurol. 2016;73:561-571. ​​​
   PubMed Web of Science ®Google Scholar
• Brinkmalm A, Brinkmalm G, Honer WG, et al. SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer’s disease. Mol Neurodegener. 2014;9:53.
   PubMed Web of Science ®Google Scholar
• Bereczki E, Francis PT, Howlett D, et al. Synaptic proteins predict cognitive decline in Alzheimer’s disease and Lewy body dementia. Alzheimers Dement. 2016;12:1149–1158.
   PubMed Web of Science ®Google Scholar
• Gilman S, Koller M, Black RS, et al. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005;64:1553–1562.
   PubMed Web of Science ®Google Scholar
• Blennow K, Zetterberg H, Rinne JO, et al. Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate Alzheimer disease. Arch Neurol. 2012;69:1002–1010.
   PubMed Web of Science ®Google Scholar
• Salloway S, Sperling R, Fox NC, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014;370:322–333.
   PubMed Web of Science ®Google Scholar
• Lachno DR, Romeo MJ, Siemers ER, et al. Validation of ELISA methods for quantification of total tau and phosporylated-tau181 in human cerebrospinal fluid with measurement in specimens from two Alzheimer’s disease studies. J Alzheimers Dis. 2011;26:531–541.
   PubMed Web of Science ®Google Scholar
• Doody RS, Thomas RG, Farlow M, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014;370:311–321.
   PubMed Web of Science ®Google Scholar
• Burstein AH, Zhao Q, Ross J, et al. Safety and pharmacology of ponezumab (PF-04360365) after a single 10-minute intravenous infusion in subjects with mild to moderate Alzheimer disease. Clin Neuropharmacol. 2013;36:8–13.
   PubMed Web of Science ®Google Scholar
• Dodel R, Rominger A, Bartenstein P, et al. Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer’s disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial. Lancet Neurol. 2013;12:233–243.
   PubMed Web of Science ®Google Scholar
• Doody RS, Raman R, Sperling RA, et al. Peripheral and central effects of gamma-secretase inhibition by semagacestat in Alzheimer’s disease. Alzheimers Res Ther. 2015;7:36.
   PubMed Web of Science ®Google Scholar
• Aisen PS, Saumier D, Briand R, et al. A phase II study targeting amyloid-beta with 3APS in mild-to-moderate Alzheimer disease. Neurology. 2006;67:1757–1763.
   PubMed Web of Science ®Google Scholar
• Lovestone S, Boada M, Dubois B, et al. A phase II trial of tideglusib in Alzheimer’s disease. J Alzheimers Dis. 2015;45:75–88.
   PubMed Web of Science ®Google Scholar
• Turner RS, Thomas RG, Craft S, et al. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology. 2015;85:1383–1391.
   PubMed Web of Science ®Google Scholar
• Coric V, van Dyck CH, Salloway S, et al. Safety and tolerability of the gamma-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol. 2012;69:1430–1440.
   PubMed Web of Science ®Google Scholar
• Galasko DR, Peskind E, Clark CM, et al. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol. 2012;69:836–841.
   PubMed Web of Science ®Google Scholar
• Johnson-Wood K, Lee M, Motter R, et al. Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease. Proc Natl Acad Sci U S A. 1997;94:1550–1555.
   PubMed Web of Science ®Google Scholar
• Salloway S, Sperling R, Gilman S, et al. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology. 2009;73:2061–2070.
   PubMed Web of Science ®Google Scholar
• Rinne JO, Brooks DJ, Rossor MN, et al. 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer’s disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol. 2010;9:363–372.
   PubMed Web of Science ®Google Scholar
• DeMattos RB, Bales KR, Cummins DJ, et al. Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A. 2001;98:8850–8855.
   PubMed Web of Science ®Google Scholar
• Portelius E, Mattsson N, Pannee J, et al. Ex vivo 18O-labeling mass spectrometry identifies a peripheral amyloid beta clearance pathway. Mol Neurodegener. 2017;12:18.
   PubMed Web of Science ®Google Scholar
• La Porte SL, Bollini SS, Lanz TA, et al. Structural basis of C-terminal beta-amyloid peptide binding by the antibody ponezumab for the treatment of Alzheimer’s disease. J Mol Biol. 2012;421:525–536.
   PubMed Web of Science ®Google Scholar
• Ostrowitzki S, Deptula D, Thurfjell L, et al. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol. 2012;69:198–207.
   PubMed Web of Science ®Google Scholar
• Henley DB, May PC, Dean RA, et al. Development of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer’s disease. Expert Opin Pharmacother. 2009;10:1657–1664.
   PubMed Web of Science ®Google Scholar
• Portelius E, Dean RA, Gustavsson MK, et al. A novel Abeta isoform pattern in CSF reflects gamma-secretase inhibition in Alzheimer disease. Alzheimers Res Ther. 2010;2:7.
   PubMed Web of Science ®Google Scholar
• Caltagirone C, Ferrannini L, Marchionni N, et al. The potential protective effect of tramiprosate (homotaurine) against Alzheimer’s disease: a review. Aging Clin Exp Res. 2012;24:580–587.
   PubMed Web of Science ®Google Scholar
• Hanger DP, Hughes K, Woodgett JR, et al. Glycogen synthase kinase-3 induces Alzheimer’s disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localisation of the kinase. Neurosci Lett. 1992;147:58–62.
   PubMed Web of Science ®Google Scholar
• Phiel CJ, Wilson CA, Lee VM, et al. GSK-3alpha regulates production of Alzheimer’s disease amyloid-beta peptides. Nature. 2003;423:435–439.
   PubMed Web of Science ®Google Scholar
• Howitz KT, Bitterman KJ, Cohen HY, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003;425:191–196.
   PubMed Web of Science ®Google Scholar
• McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology. 1984;34:939–944.
   PubMed Web of Science ®Google Scholar
• Landau SM, Horng A, Fero A, et al. Amyloid negativity in patients with clinically diagnosed Alzheimer disease and MCI. Neurology. 2016;86:1377–1385.
   PubMed Web of Science ®Google Scholar
• Beach TG, Monsell SE, Phillips LE, et al. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010. J Neuropathol Exp Neurol. 2012;71:266–273.
   PubMed Web of Science ®Google Scholar
• Sevigny J, Chiao P, Bussiere T, et al. The antibody aducanumab reduces Abeta plaques in Alzheimer’s disease. Nature. 2016;537:50–56.
   PubMed Web of Science ®Google Scholar
• Bateman RJ, Siemers ER, Mawuenyega KG, et al. A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system. Ann Neurol. 2009;66:48–54.
   PubMed Web of Science ®Google Scholar