@article{a91444cf6eec4a9bb39ed672f897b4cb,
title = "APOE ε4 carriers may undergo synaptic damage conferring risk of Alzheimer's disease",
abstract = "Introduction Pathogenesis of Alzheimer's disease (AD) in apolipoprotein E ε4 (APOE ε4) carriers remains unclear. We hypothesize that APOE isoforms have differential effects on synaptic function. Methods We compared levels of CSF neurogranin (Ng) between APOE ε4 carriers and noncarriers in 399 subjects with normal cognition, mild cognitive impairment (MCI), and AD. We examined associations between Ng levels and age, education, gender, CSF-Aβ42, and tau protein. Results Neurogranin levels were significantly higher in APOE ε4 carriers compared to APOE ε4 noncarriers with MCI. Levels of Ng between the APOE ε4 carriers and APOE ε4 noncarriers with AD did not differ. Ng levels were correlated with MMSE and levels of tau and Aβ42. Discussion Significantly higher CSF Ng levels in APOE ε4 carriers with MCI may reflect synaptic injury underlying early cognitive impairment. Neurogranin may be an early biomarker of AD and important for disease diagnosis and timing of intervention in APOE ε4 carriers.",
keywords = "APOE, APOE ε4, Alzheimer's disease, Mild cognitive impairment, Neurogranin, Synaptic function",
author = "{Alzheimer's Disease Neuroimaging Initiative} and Xiaoyan Sun and Chuanhui Dong and Bonnie Levin and Elizabeth Crocco and David Loewenstein and Henrik Zetterberg and Kaj Blennow and Wright, {Clinton B.}",
note = "Funding Information: Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Funding Information: Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) ( National Institutes of Health Grant U01 AG024904 ) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012 ). ADNI is funded by the National Institute on Aging , the National Institute of Biomedical Imaging and Bioengineering , and through generous contributions from the following: AbbVie , Alzheimer's Association ; Alzheimer's Drug Discovery Foundation ; Araclon Biotech ; BioClinica, Inc. ; Biogen ; Bristol-Myers Squibb Company ; CereSpir, Inc. ; Eisai ; Elan Pharmaceuticals, Inc. ; Eli Lilly and Company ; EuroImmun ; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc. ; Fujirebio ; GE Healthcare ; IXICO Ltd. ; Janssen Alzheimer Immunotherapy Research & Development, LLC. ; Johnson & Johnson Pharmaceutical Research & Development LLC. ; Lumosity ; Lundbeck ; Merck & Co., Inc. ; Meso Scale Diagnostics, LLC. ; NeuroRx Research ; Neurotrack Technologies ; Novartis Pharmaceuticals Corporation ; Pfizer Inc. ; Piramal Imaging ; Servier ; Takeda Pharmaceutical Company ; and Transition Therapeutics . The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education , and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Publisher Copyright: {\textcopyright} 2016 The Alzheimer's Association",
year = "2016",
month = nov,
day = "1",
doi = "10.1016/j.jalz.2016.05.003",
language = "English (US)",
volume = "12",
pages = "1159--1166",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "11",
}