DEPOSITION OF BETA/A4 PROTEIN ALONG NEURONAL PLASMA-MEMBRANES IN DIFFUSE SENILE PLAQUES

被引:109
作者
PROBST, A
LANGUI, D
IPSEN, S
ROBAKIS, N
ULRICH, J
机构
[1] CUNY MT SINAI SCH MED, DEPT PSYCHIAT, NEW YORK, NY 10029 USA
[2] CUNY MT SINAI SCH MED, CTR NEUROBIOL, NEW YORK, NY 10029 USA
关键词
DIFFUSE PLAQUES; DENDRITES; SYNAPSES; BETA/A4; PROTEIN; AMYLOID PRECURSOR PROTEIN;
D O I
10.1007/BF00294426
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The origin of the extracellular beta-amyloid protein (beta/A4) found in senile plaques and the cellular mechanisms responsible for its deposition in cerebral tissues are still an unresolved issue in Alzheimer's disease. In this study we analyzed in detail the distribution of various epitopes of beta/A4 in relation to local cellular elements in diffuse plaques of the hippocampal region. We also correlated our findings with the presence and distribution of non-beta/A4 epitopes of the amyloid precursor protein (APP) and with synaptophysin immunoreactivity in the cortical neuropil. Discontinuous beta/A4-immunoreactive deposits were found along dendrites, and around the soma of neurons included in the plaques. Furthermore, increased synaptophysin reactivity with slightly dilated synaptophysin-immunolabeled presynaptic terminals were found in diffuse plaques. APP epitopes could not be found in diffuse plaques. However, some of the APP antibodies, mainly those to the C-terminal portion of APP, and antibodies to beta/A4 recognized clusters of flat vesicular profiles (0.6-1.4-mu-m in width and 2-3-mu-m in length) in the neuropil of cortical areas where plaques had developed. Our findings are compatible with a neuronal origin of beta/A4 in diffuse plaques and with a primary release of beta/A4 at synaptic sites along the immunostained neurites. They also suggest that diffuse plaques might be preceded by minute lesions of the neuropil where beta/A4 is not yet released from the precursor molecule.
引用
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页码:21 / 29
页数:9
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