期刊
NEUROBIOLOGY OF AGING
卷 97, 期 -, 页码 1-9出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2020.06.007
关键词
Alzheimer's disease; Mild cognitive impairment; Amyloid-beta; Aquaporin-4; Glymphatic system
资金
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [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
- Canadian Institutes of Health Research
- Michael J Fox Foundation
- Edmond and Lilly Safra Foundation
- CHDI Foundation
- Glaxo Wellcome RD
- Life Molecular Imaging
- Invicro
- Curium
- Medical Research Council (UK)
- AVID radiopharmaceuticals
- National Institute for Health Research
- Alzheimer's Research UK
- European Commission IMI2 fund
The study found that genetic variation of the AQP4 gene is associated with Aβ uptake, neuropathology, clinical outcomes, and cognitive decline, serving as a potential biomarker for predicting disease burden in patients on the dementia spectrum.
Clearance of amyloid-beta (A beta) from the brain is hypothesized to be mediated by the glymphatic system through aquaporin-4 (AQP4) water channels. Genetic variation of AQP4 may impact water channel function, A beta clearance, and clinical outcomes. We examined whether single-nucleotide polymorphisms (SNPs) of the AQP4 gene were related to A beta neuropathology on [F-18]Florbetapir PET in 100 A beta positive late mild cognitive impairment (LMCI) or Alzheimer's disease (AD) patients and were predictive of clinical outcome in prodromal AD patients. AQP4 SNP rs72878794 was associated with decreased A beta uptake, whereas rs151244 was associated with increased A beta uptake, increased risk of conversion from MCI and LMCI to AD, and an increased 4-year rate of cognitive decline in LMCI. AQP4 genetic variation was associated with A beta accumulation, disease stage progression, and cognitive decline. This variation may correspond to changes in glymphatic system functioning and brain A beta clearance and could be a useful biomarker in predicting disease burden for those on the dementia spectrum. (C) 2020 Elsevier Inc. All rights reserved.
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