期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 290, 期 28, 页码 17415-17438出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M115.643577
关键词
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资金
- National Institutes of Health
- BrightFocus Foundation
- Alzheimer's Association
- Falk Medical Research Trust
Alzheimer disease (AD) is characterized by amyloid-beta accumulation, with soluble oligomers (A beta o) being the most synaptotoxic. However, the multivalent and unstable nature of A beta o limits molecular characterization and hinders research reproducibility. Here, we characterized multiple A beta o forms throughout the life span of various AD mice and in post-mortem human brain. A beta o exists in several populations, where prion protein (PrPC)-interacting A beta o is a high molecular weight A beta assembly present in multiple mice and humans with AD. Levels of PrPC-interacting A beta o match closely with mouse memory and are equal or superior to other A beta measures in predicting behavioral impairment. However, A beta o metrics vary considerably between mouse strains. Deleting PrPC expression in mice with relatively low PrPC-interacting A beta o (Tg2576) results in partial rescue of cognitive performance as opposed to complete recovery in animals with a high percentage of PrPC-interacting A beta o (APP/PSEN1). These findings highlight the relative contributions and interplay of A beta o forms in AD.
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