Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease

• Satoh Jun-ichi

  Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University

• Kino Yoshihiro

  Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University

• Yanaizu Motoaki

  Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University

• Tosaki Youhei

  Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University

• Sakai Kenji

  Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University

• Ishida Tsuyoshi

  Department of Pathology and Laboratory Medicine, Kohnodai Hospital, NCGM

• Saito Yuko

  Department of Laboratory Medicine, National Center Hospital, NCNP

Abstract

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).

Journal

• Intractable & Rare Diseases Research

  Intractable & Rare Diseases Research 6 (4), 262-268, 2017

  International Research and Cooperation Association for Bio & Socio-Sciences Advancement

Keywords

• ABI3
• Alzheimer's disease
• leukoencephalopathy
• microglia
• Nasu-Hakola disease

Details

• CRID: 1390001205544429568
• NII Article ID: 130006252922
• DOI: 10.5582/irdr.2017.01073
• ISSN: 2186361X
• ISSN: 21863644
• Web Site: https://www.jstage.jst.go.jp/article/irdr/6/4/6_2017.01073/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2019068914
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed