期刊
INTRACTABLE & RARE DISEASES RESEARCH
卷 6, 期 4, 页码 262-268出版社
INT RESEARCH & COOPERATION ASSOC BIO & SOCIO-SCIENCES ADVANCEMENT
DOI: 10.5582/irdr.2017.01073
关键词
ABI3; Alzheimer's disease; leukoencephalopathy; microglia; Nasu-Hakola disease
资金
- Research on Intractable Diseases [H21-Nanchi-Ippan-201, H22-Nanchi-Ippan-136]
- Ministry of Health, Labour and Welfare of Japan
- JSPS KAKENHI [C25430054, 16K07043]
- Dementia Drug Development Research Center (DRC) project [S1511016]
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan
- Grants-in-Aid for Scientific Research [16K07043, 16K09683] Funding Source: KAKEN
Nasu-Hakola disease (NHD) is a rare autosomal recessive leukoencephalopathy caused by a loss-of-function mutation of either TYROBP (DAP12) or TREM2 expressed in microglia. A rare variant of the TREM2 gene encoding p. Arg47His causes a 3-fold increase in the risk for late-onset Alzheimer's disease (LOAD). A recent study demonstrated that a rare coding variant p. Ser209Phe in the ABI family member 3 (ABI3) gene, a regulator of actin cytoskeleton organization, confers risk of developing of LOAD, although the pattern of ABI3 expression in AD and NHD brains with relevance to microglial pathology remains to be characterized. We investigated the cell type-specific expression of ABI3 in the brains derived from four non-neurological controls (NC), ten AD and five NHD cases by immunohistochemistry. We identified an intense ABI3 immunoreactivity chiefly on a subset of microglia with ramified or amoeboid morphology located in the grey matter and the white matter of the frontal cortex and the hippocampus of NC, AD, and NHD cases. The immunolabeled area of ABI3-positive microglia was not significantly different among NC, AD, and NHD cases due to great variability from case to case. The clusters of ABI3-immunoreactive microglia were found exclusively in AD brains and they were associated with amyloid plaques. Although these observations do not actively support the view that ABI3-immunoreactive microglia play a central role in the development of leukoencephalopathy in NHD brains and the neurodegeneration in AD brains, the intense expression of ABI3 on microglia might regulate their migration under conditions of health and disease in the central nervous system (CNS).
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