Title |
Age and amyloid effects on human central nervous system amyloid‐beta kinetics
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Published in |
Annals of Neurology, July 2015
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DOI | 10.1002/ana.24454 |
Pubmed ID | |
Authors |
Bruce W Patterson, Donald L Elbert, Kwasi G Mawuenyega, Tom Kasten, Vitaliy Ovod, Shengmei Ma, Chengjie Xiong, Robert Chott, Kevin Yarasheski, Wendy Sigurdson, Lily Zhang, Alison Goate, Tammie Benzinger, John C Morris, David Holtzman, Randall J Bateman |
Abstract |
Age is the single greatest risk factor for Alzheimer's disease with the incidence doubling every 5 years after age 65. However, our understanding of the mechanistic relationship between increasing age and the risk for Alzheimer's disease is currently limited. We therefore sought to determine the relationship between age, amyloidosis, and amyloid-beta kinetics in the central nervous system (CNS) of humans Methods: Amyloid-beta kinetics were analyzed in 112 participants and compared to the ages of participants and the amount of amyloid deposition. We found a highly significant correlation between increasing age and slowed amyloid-beta turnover rates (2.5-fold longer half-life over five decades of age). In addition, we found independent effects on amyloid-beta42 kinetics specifically in participants with amyloid deposition. Amyloidosis was associated with a higher (>50%) irreversible loss of soluble amyloid-beta42 and a 10-fold higher amyloid-beta42 reversible exchange rate. These findings reveal a mechanistic link between human aging and the risk of amyloidosis which may be due to a dramatic slowing of amyloid-beta turnover, increasing the likelihood of protein misfolding that leads to deposition. Alterations in amyloid-beta kinetics associated with aging and amyloidosis suggest opportunities for diagnostic and therapeutic strategies. More generally, this study provides an example of how changes in protein turnover kinetics can be used to detect physiologic and pathophysiologic changes and may be applicable to other proteinopathies. This article is protected by copyright. All rights reserved. |
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Mendeley readers
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Researcher | 40 | 25% |
Student > Ph. D. Student | 24 | 15% |
Student > Master | 13 | 8% |
Student > Bachelor | 12 | 8% |
Professor > Associate Professor | 11 | 7% |
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Biochemistry, Genetics and Molecular Biology | 10 | 6% |
Other | 26 | 16% |
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