期刊
NEUROSCIENCE LETTERS
卷 771, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2021.136419
关键词
Alzheimer 's disease; CD2AP; Rs9296559; Tau; Cerebrospinal fluid tau
资金
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Cogstate
- Eisai Inc.
- 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 and Development, LLC
- Johnson and Johnson Pharmaceutical Research and Development LLC
- Lumosity
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- National Natural Science Foundation of China [81970998]
- Key Research and Development project of Zhejiang Province [2019C03039]
- Natural Science Foundation of Zhejiang province [LBY21H090003]
- Lundbeck
- Merck and Co., Inc.
- Meso Scale Diagnostics, LLC
The study found that rs9296559 was associated with higher levels of CSF t-tau and p-tau in MCI patients, suggesting that CD2AP modifies AD risk by altering tau-related neurodegeneration. This is the first study to evaluate the association between CD2AP genotypes and AD CSF biomarkers.
Introduction: Rs9296559 within CD2-associated protein (CD2AP) has been identified as a susceptibility locus for Alzheimer's disease (AD). Recent studies indicated that CD2AP functioned as a regulator of endocytic trafficking to modulate the beta-amyloid (A beta) generation in neurons. Moreover, knockdown of cindr, the Drosophila ortholog of CD2AP, enhanced tau-induced neurodegeneration, implying CD2AP also participated in tau pathology. However, the role of rs9296559 in regulating A beta and tau metabolism in AD was still unclear. Methods: Here, the associations of rs9296559 with CSF A beta 1-42, p-tau, and t-tau were performed using a linear regression model in a total of 543 cognitive normal (CN), mild cognitive impairment (MCI), and AD subjects from the Alzheimer's disease Neuroimaging Initiative (ADNI) cohort. The results were replicated in an independent cohort consisting of 198 Chinese subjects recruited from our hospital. Results: In the ADNI cohort, CC + TC genotypes significantly increased CSF t-tau and p-tau levels in MCI patients but did not alter CSF tau levels in AD. This association was also observed in the replication cohort. Moreover, there was no association between rs9296559 and CSF A beta 1-42 level at different disease statuses in the two cohorts. Conclusion: Our findings showed that rs9296559 was associated with higher CSF t-tau and p-tau levels in MCI, supporting that CD2AP modified AD risk by altering tau-related neurodegeneration in the early stage of the AD continuum. To the best of our knowledge, this is the first study to evaluate the association between CD2AP genotypes and AD CSF biomarkers.
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