Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer's disease

Abstract

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Potential Conflicts of Interest S.E.S. has a family member with stock in Eli Lilly, which is developing drugs for Alzheimer disease. D.L.G. is a full time employee at Biogen, which funded this study and is developing drugs for Alzheimer disease. L.M.S. receives research support from Eli Lilly, Hoffman LaRoche, MJFox Foundation for Parkinson's Research for Biofind study and has served as consultant and/or advisory boards for Roche Diagnostics and Eli Lilly. He provides quality control oversight for Roche Elecsys immunoassays in the ADNI study. J.J.H. is on the advisory board and consults for both Biogen and Lundbeck A/S. T.L.S.B. consults for Eli Lilly and receives research funding from Avid Radiopharmaceuticals. J.L. reports personal fees from Aesku, Bayer Vital, the Willi Gross Foundation, Axon Neuroscience, and Ionis Pharmaceuticals. He has received non-financial support from AbbVie that is outside the submitted work. D.M.H. co-founded and is on the scientific advisory board of C 2 N Diagnostics. D.M.H. consults for Genentech, AbbVie, Eli Lilly, Proclara, and Denali. Washington University receives research grants to the lab of D.M.H. from C2N Diagnostics, Eli Lilly, AbbVie, and Denali. J.H.L. reports being named on patents related to the use of VILIP-1. These are being managed by Washington University in accordance with University policy. J.H.L. is a co-inventor on patent 11/630582 (2005) (Markers for brain damage) and patent 60957132 (2008) (Alzheimer's diagnosis). J.C.M. has or is currently participating in clinical trials of anti-dementia drugs sponsored by Janssen Immunotherapy, Eli Lilly and Company, and Pfizer. He has served as a consultant for or has received speaking honoraria from Eisai, Esteve, Janssen Alzheimer Immunotherapy Program/Elan, GlaxoSmithKline, Novartis, and Pfizer. He receives research support from Eli Lilly/Avid Radiopharmaceuticals. R.J.B. co-founded and is on the scientific advisory board of C 2 N Diagnostics. He consults for Roche, Genentech, AbbVie, Pfizer, Boehringer-Ingelheim, and Merck. A.M.F. has received research funding from Biogen, Fujirebio and Roche Diagnostics. She is a member of the scientific advisory boards for Roche, Genentech and AbbVie and also consults for Araclon/Griffols and DiamiR.

Cerebrospinal Fluid YKL-40 and Neurogranin in Familial Alzheimer’s Disease: A Pilot Study

“…The MC for which levels of YKL-40 were available had an average of 12 years left to the expected onset of first clinical symptoms, while the MC subgroup, having enough sample volume to analyze neurogranin as well, had an average of 10 years left to expected symptom onset. Regarding CSF YKL-40, these results are not in concordance with the results of a large study on CSF biomarkers in the Dominantly Inherited Alzheimer Network (DIAN), which showed an increase in CSF YKL-40 in FAD mutation carriers 15-19 years before the expected onset of clinical symptoms [60]. No presymptomatic change in CSF neurogranin was observed in the DIAN study, which is in agreement with the result obtained in the current study.…”

Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease

“…6 of 13 EMBO Molecular Medicine 11: e11170 | 2019 ª 2019 The Authors earlier change in Ab42 is not supported by a recent study on autosomal dominant AD (Schindler et al, 2019). The Ab40 finding should also be interpreted cautiously since this initial decline was driven by few individuals and the Ab40 model was barely significant for CSF (P = 0.02; Appendix Fig S1) and was not significant for plasma (P = 0.37; Appendix Fig S2).…”

New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer’s disease

“…increased NFL: most strongly associated with the dementia stage of AD ▪ These are complementary to each other in AD clinical staging CSF neurogranin, NFL 94 ▪ NFL: highest accuracy in prediction of MCI conversion to AD compared to neurogranin, Aβ 42 , pTau 181 , and tTau levels, on >1 yr FU CSF neurogranin, SNAP-25, VILIP-1, YKL-40 9,98 ▪ commonly cooccur with AD 7 , considering both diseasespecific and more general biomarkers of pathology may increase the likelihood of realizing efficient diseasemodifying therapeutics. This approach could lead to more efficient treatment regimens and allow monitoring of the response to treatment on an individual patient basis, which is important given the diversity of AD pathology.…”