期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：16
页码：6820-6825
DOI：10.1073/pnas.0900345106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Fibrillar amyloid-beta (A{beta}) is found in the brains of many cognitively normal older people. Whether or not this reflects a predisposition to Alzheimer's disease (AD) is unknown. We used Pittsburgh Compound B (PiB) PET to characterize the relationship between fibrillar A{beta} burden and this predisposition in cognitively normal older people at 3 mean levels of genetic risk for AD. Dynamic PiB PET scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest (ROIs) were used to characterize and compare cerebral-to-cerebellar PIB distribution volume ratios, reflecting fibrillar A{beta} burden, in 28 cognitively normal persons (mean age, 64 years) with a reported family history of AD and 2 copies, 1 copy, and no copies of the apolipoprotein E (APOE) {varepsilon}4 allele. The 8 {varepsilon}4 homozygotes, 8 heterozygotes, and 12 noncarriers did not differ significantly in terms of age, sex, or cognitive scores. Fibrillar A{beta} was significantly associated with APOE {varepsilon}4 carrier status and {varepsilon}4 gene dose in AD-affected mean cortical, frontal, temporal, posterior cingulate-precuneus, parietal, and basal ganglia ROIs, and was highest in an additional homozygote who had recently developed mild cognitive impairment. These findings suggest that fibrillar A{beta} burden in cognitively normal older people is associated with APOE {varepsilon}4 gene dose, the major genetic risk factor for AD. Additional studies are needed to track fibrillar A{beta} accumulation in persons with different kinds and levels of AD risk; to determine the extent to which fibrillar A{beta
