期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 65, 期 3, 页码 781-791出版社
IOS PRESS
DOI: 10.3233/JAD-170064
关键词
Alzheimer's disease; amyloid-beta PET; ApoE4; body mass index; FDG-PET; markers of AD pathology
资金
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- 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
- 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
- Transition Therapeutics
- Canadian Institutes of Health Research
- National Institute of Biomedical Imaging and Bioengineering
Body weight loss in late-life is known to occur at a very early stage of Alzheimer's disease (AD). Apolipoprotein E4 (ApoE4) represents a major genetic risk factor for AD and is linked to an increased cortical amyloid-beta (A beta) accumulation. Since the relationship between body weight, ApoE4, and AD pathology is poorly investigated, we aimed to evaluate whether ApoE4 allelic status modifies the association of body mass index (BMI) with markers of AD pathology. A total of 368 A beta-positive cognitively healthy or mild cognitive impaired subjects had undergone [F-18]-AV45-PET, [F-18]-FDG-PET, and T1w-MRI examinations. Composite cortical [F-18]-AV45 uptake and [F-18]-FDG uptake in posterior cingulate cortex were calculated as surrogates of cortical A beta load and glucose metabolism, respectively. Multiple linear regressions were performed to assess the relationships between these PET biomarkers with BMI, present cognitive performance, and cognitive changes over time. Multivariate analysis of covariance was conducted to test for statistical differences between ApoE4/BMI categories on the PET markers and cognitive scores. In carriers of the ApoE4 allele only, BMI was inversely associated with cortical amlyoid load (beta = -0.193, p < 0.005) and recent cognitive decline (beta = -0.209, p < 0.05), and positively associated with cortical glucose metabolism in an AD-vulnerable region (beta = 0.145, p< 0.05). ApoE4/BMI category analyses demonstrated lower A beta load, higher posterior cingulate glucose metabolism, improved cognitive performance, and lower progression of cognitive decline in obese ApoE4 carriers. The effect of ApoE4 in promoting the accumulation of cortical amyoid, which may itself be a driver for weight loss, may be moderated by altering leptin signaling in the hypothalamus.
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