Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease

Eric M. Reiman, Kewei Chen, Xiaofen Liu, Daniel Bandy, Meixiang Yu, Wendy Lee, Napatkamon Ayutyanont, Jennifer Keppler, Stephanie A. Reeder, Jessica B S Langbaum, Gene E. Alexander, William E. Klunk, Chester A. Mathis, Julie C. Price, Howard J. Aizensteini, Steven T. DeKosky, Richard John Caselli

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Abstract

Fibrillar amyloid-beta (Aβ) is found in the brains of many cogni-tively 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 Aβ 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 Aβ 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) ε4 allele. The 8 ε4 homozygotes, 8 heterozygotes, and 12 noncarriers did not differ significantly in terms of age, sex, or cognitive scores. Fibrillar Aβ was significantly associated with APOE ε4 carrier status and ε4 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 Aβ burden in cognitively normal older people is associated with APOE ε4 gene dose, the major genetic risk factor for AD. Additional studies are needed to track fibrillar Aβ accumulation in persons with different kinds and levels of AD risk; to determine the extent to which fibrillar Aβ, alone or in combination with other biomarkers and risk factors, predicts rates of cognitive decline and conversion to clinical AD; and to establish the role of fibrillar Aβ imaging in primary prevention trials.

Original languageEnglish (US)
Pages (from-to)6820-6825
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number16
DOIs
StatePublished - Apr 21 2009

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Keywords

  • Apolipoprotein E
  • Pittsburgh compound B pet

ASJC Scopus subject areas

  • General

Cite this

Reiman, E. M., Chen, K., Liu, X., Bandy, D., Yu, M., Lee, W., Ayutyanont, N., Keppler, J., Reeder, S. A., Langbaum, J. B. S., Alexander, G. E., Klunk, W. E., Mathis, C. A., Price, J. C., Aizensteini, H. J., DeKosky, S. T., & Caselli, R. J. (2009). Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 106(16), 6820-6825. https://doi.org/10.1073/pnas.0900345106