期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 177, 期 1, 页码 325-333出版社
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2010.090937
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资金
- Alzheimer's Association [IIRG-2366]
- Dana Foundation
The amyloid-p peptide (A beta) deposited in plaques in Alzheimer's disease has been shown to cause degeneration of neurons in experimental paradigms in vivo and in vitro. However, it has been difficult to convincingly demonstrate toxicity of native amyloid deposits in the aged and Alzheimer brains. Here we provide evidence that the fibrillar conformation of A beta (fA beta) deposited in compact plaques is associated with the pathologies observed in Alzheimer brains. fA beta containing compact but not diffuse plaques in the aged rhesus cortex contained activated microglia and clusters of phosphorylated tau-positive swollen neurites. Scholl's quantitative analysis revealed that the area adjacent to fA beta, containing compact but not diffuse plaques in aged rhesus, aged human, and Alzheimer's disease cortex, displays significant loss of neurons and small but statistically significant reduction in the density of cholinergic axons. These observations suggest that fA beta toxicity may not be restricted to cultured cells and animal injection models. Rather, fA beta deposited in native compact plaques in aged and AD brains may exert selective toxic effects on its surrounding neural environment. (Am J Pathol 2010, 177:325-333; DOI: 10.2353/ajpath.2010.090937)
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