@article{f318fd92fd594e828817b6aab609158c,
title = "Identification of the Aβ37/42 peptide ratio in CSF as an improved Aβ biomarker for Alzheimer's disease",
abstract = "Introduction: Identifying CSF-based biomarkers for the β-amyloidosis that initiates Alzheimer's disease (AD) could provide inexpensive and dynamic tests to distinguish AD from normal aging and predict future cognitive decline. Methods: We developed immunoassays specifically detecting all C-terminal variants of secreted amyloid β-protein and identified a novel biomarker, the Aβ 37/42 ratio, that outperforms the canonical Aβ42/40 ratio as a means to evaluate the γ-secretase activity and brain Aβ accumulation. Results: We show that Aβ 37/42 can distinguish physiological and pathological status in (1) presenilin-1 mutant vs wild-type cultured cells, (2) AD vs control brain tissue, and (3) AD versus cognitively normal (CN) subjects in CSF, where 37/42 (AUC 0.9622) outperformed 42/40 (AUC 0.8651) in distinguishing CN from AD. Discussion: We conclude that the Aβ 37/42 ratio sensitively detects presenilin/γ-secretase dysfunction and better distinguishes CN from AD than Aβ42/40 in CSF. Measuring this novel ratio alongside promising phospho-tau analytes may provide highly discriminatory fluid biomarkers for AD.",
keywords = "Alzheimer's disease, CSF biomarkers, amyloid β-protein",
author = "{Dominantly Inherited Alzheimer Network (DIAN)} and Lei Liu and Lauro, {Bianca M.} and Amy He and Hyo Lee and Sanjay Bhattarai and Wolfe, {Michael S.} and Bennett, {David A.} and Karch, {Celeste M.} and Tracy Young-Pearse and Selkoe, {Dennis J.}",
note = "Funding Information: We are grateful to members of the Selkoe laboratory for helpful discussions. We thank Dr. R. Petersen and colleagues, Mayo Clinic, Rochester, MN for generously providing CSF samples. Data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer Network (DIAN, U19AG032438) funded by the National Institute on Aging (NIA),the Alzheimer's Association (SG‐20‐690363‐DIAN), the German Center for Neurodegenerative Diseases (DZNE), Raul Carrea Institute for Neurological Research (FLENI), Partial support by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development, AMED, and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), Spanish Institute of Health Carlos III (ISCIII), Canadian Institutes of Health Research (CIHR), Canadian Consortium of Neurodegeneration and Aging, Brain Canada Foundation, and Fonds de Recherche du Qu{\'e}bec – Sant{\'e}. This manuscript has been reviewed by DIAN Study investigators for scientific content and consistency of data interpretation with previous DIAN Study publications. We acknowledge the altruism of the participants and their families and contributions of the DIAN research and support staff at each of the participating sites for their contributions to this study.This work was funded by the following NIH grants: R01 AG06173 (DJS), R01 AG071865 (DJS and LL), PPG AG015379 (DJS), R01 AG055909 (TYP) and R03 AG063046 (LL). The brain tissue results published here are in whole or in part based on data obtained from the AMP‐AD Knowledge Portal (https://adknowledgeportal.synapse.org/ ). Study data were provided by the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago. ROS‐MAP data collection was supported through funding by NIA grants P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984, U01AG46152, the Illinois Department of Public Health, and the Translational Genomics Research Institute. This work was funded by National Institutes of Health grants R01 AG006173 (DJS), R01 AG071865 (DJS and LL) and P01 AG015379 (DJS), R01 AG055909 (TYP), and the Davis APP program at BWH (DJS). LL was supported by the National Institutes of Health grant R03AG063046, a MADRC development project grant, and a BWH Program for Interdisciplinary Neuroscience pilot grant. The funders had no role in data collection, analysis, or decision to publish. Publisher Copyright: {\textcopyright} 2022 the Alzheimer's Association",
year = "2022",
doi = "10.1002/alz.12646",
language = "English",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
}