| Co-Investigator(Kenkyū-buntansha) |
KAMETANI Fuyuki PRIT, Dept. of Molecular Biology, Researcher, 分子生物学研究室, 研究員 (70186013)
TOKUTAKE Sotoshi PRIT, Dept. of Molecular Biology, Researcher, 分子生物学研究室, 主任研究員 (50090402)
SHINODA Tomotaka Tokyo Metropolitan Univ. Dept. of Chemistry, Faculty of Science, Associate profe, 理学部化学教室, 助教授 (50000253)
OYANAGI Shinsaku PRIT, Dept. of Ultrastructure, Chief, 超微形態研究室, 参事研究員 (50018595)
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| Research Abstract |
The deposition of amyloid is considered to be one of the most characteristic chemical and pathological hallmarks in the Alzheimer (AD) or Down syndrome (DS) brains. To identify subsequences of amyloid precursor protein (APP) in the AD and control brains, western blots and immunohistochemistry were performed using 6 antibodies against synthetic peptides (subsequences of APP; R35, residues 274-286; R36, residues 527-540; R37, residues 681-695; beta protein, residues 597-620; protein inhibitor domains (PID), residues 325-337, 351-364 (Kitaguchi et al., 1988) on cryostat sections of cerebral cortex and hippocampus of the AD brain and of age-matched controls. Western blots detected all of these peptides, except for PID, in AD as well as in control brains. However, immunohistochemistry could detect only R36 and beta protein in amyloid and R37 (C-terminal of APP) in what may be degenerated neurites in the periphery of senile plaques.
A sensitive methenamine silver/Nissl stain disclosed that pr
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eamyloid were found immediately adjacent to, or around the cell bodies of neurons. We consider an early stage of senile plaque formation to be the deposition of preamyloid substance adjacent to the cell body of neurons. We suggest that the amyloid progressively accumulates around the cell body until the enclosed neuron degenerates.
A monoclonal antibody, termed AD11/8 which is reactive to microglial cells, stains numerous microglial cells intensively and they often formed clusters in gray matter in AD brain. By double immunostaining with AD11/8 and a polyclonal antibody against synthetic amyloid beta protein, clustered microglial cells were observed. in and around senile plaques with amyloid deposits. These results indicate that microglial cells may play an important role in senile plaque formation.
A monoclonal antibody HY20 which stains amyloid deposits in the AD brain, specifically reacted with the variable region of a lambda light chain of human immunoglobulins. It is concluded that an epitope shared with a lambda light chain is included in or associated with amyloid deposits in the AD brain.
These data suggest that an immunological mechanism is involved in the amyloid formation in senile plaques in AD brain. Less
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