2000 Fiscal Year Final Research Report Summary
An immunohistochemical study on Alzheimer change and neuronal death
| Project/Area Number |
11670937
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Kanazawa University |
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Principal Investigator |
KOBAYASHI Katsuji Kanazawa University, Department of Neuropsychiatry, Associated Professor, 医学部・附属病院, 講師 (50221239)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUTANI Yuken Fukui Medical University, Department of Neuropsychiatry, Assistant Professor, 附属病院, 助教授 (10273004)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Alzheimer's disease / Senile plaques / Neurofibrillary tangles / Apoptosis / White matter / Astrocytes / Oligodendrocytes |
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| Research Abstract |
In the present study, we studied the relationship between neuronal death and occurrence of senile plaques and neurofibrillary changes. Apoptotic cells were observed in the endothelial cell of small vessels with angiopathic change and neurons and glial cells around the classic senile plaques. As for neurofibrillary changes and apoptosis, the intensity of AT8 tau immunoreactivity and the number of apoptotic cells were significantly correlated, in particular, the number of apoptotic cells significantly correlated with that of extracellular neurofibrillary tangles labeled with C4d and CD68. Immunoreactivity of C4d and amyloid P appeared to develop after apoptotic changes. Triplet labeling of Gallyas silver impregnation/ AT8 tau labeling/. TUNEL showed that occurrence of silver-stained neurofibrillary tangles in the AT8tau-positive cytoplasms contributed to the development of TUNEL-positive nuclei. Senile plaques with amyloid fibrils contained apoptotic cells around them, while the diffuse
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plaques contained few apoptotic cells. Quantitative correlation between density of senile plaques labeled with ubiquitin and apoptotic cells was not definite. Statistical analysis revealed that density of apoptotic cells correlated more significantly with density of senile plaques than that of neurofibrillary tangles. Non-ischemic white matter lesions in Alzheimer cases contained considerable numbers of apoptotic glial cells. They were largely astrocytes and oligodendrocytes. Many white matter astrocytes displayed regressive changes in which intracytoplasmic vacuoles were labeled with CD68. The astrocytes with regressive changes were apoptotic without exception, and these astrocytes were distributed predominantly in the temporal white matter. The density of apoptotic white matter endothelial cell was not different between temporal and frontal white matter. In summary, apoptosis of neurons and glial cells could be closely associated with beta amyloid protein deposits, CD68KP1-positive materials were found in the white matter astrocytes with regressive changes and apoptosis, and numerous oligodendrocytes were apoptotic. A role of glial apoptosis for white matter lesions in Alzheimer's diseased brains remains to be determined. Less
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