期刊
JOURNAL OF NEUROSCIENCE
卷 21, 期 2, 页码 372-381出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.21-02-00372.2001
关键词
Alzheimer's disease; neurodegeneration; Tg2576 transgenic animal model; amyloid beta protein; cerebrospinal fluid; plasma
资金
- NIA NIH HHS [AG15453, P01 AG015453] Funding Source: Medline
The accumulation of amyloid beta protein (A beta) in the Tg2576 mouse model of Alzheimer's disease (AD) was evaluated by ELISA, immunoblotting, and immunocytochemistry. Changes in A beta begin at 6-7 months as SDS-insoluble forms of A beta 42 and A beta 40 that require formic acid for solubilization appear. From 6 to 10 months, these insoluble forms increase exponentially. As insoluble A beta appears, SDS-soluble A beta decreases slightly, suggesting that it may be converting to an insoluble form. Our data indicate that it is full-length unmodified A beta that accumulates initially in Tg2576 brain. SDS-resistant A beta oligomers and most A beta species that are N-terminally truncated or modified develop only in older Tg2576 mice, in which they are present at levels far lower than in human AD brain. Between 6 and 10 months, when SDS-insoluble A beta 42 and A beta 40 are easily detected in every animal, histopathology is minimal because only isolated A beta cores can be identified. By 12 months, diffuse plaques are evident. From 12 to 23 months, diffuse plaques, neuritic plaques with amyloid cores, and biochemically extracted A beta 42 and A beta 40 increase to levels like those observed in AD brains. Coincident with the marked deposition of A beta in brain, there is a decrease in CSF A beta and a substantial, highly significant decrease in plasma A beta. If a similar decline occurs in human plasma, it is possible that measurement of plasma A beta may be useful as a premorbid biomarker for AD.
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