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Curr Opin Neurobiol. 2016 Feb;36:74-81. doi: 10.1016/j.conb.2015.10.004. Epub 2015 Oct 24.

Microglial genes regulating neuroinflammation in the progression of Alzheimer's disease.

Author information

1
Department of Neuroinflammation, University College London, Institute of Neurology, 1 Wakefield Street, London WC1 N 1PK, UK; Department of Molecular Neuroscience, University College London, Institute of Neurology, 1 Wakefield Street, London WC1 N 1PK, UK.
2
Department of Neuroinflammation, University College London, Institute of Neurology, 1 Wakefield Street, London WC1 N 1PK, UK.
3
Department of Molecular Neuroscience, University College London, Institute of Neurology, 1 Wakefield Street, London WC1 N 1PK, UK.
4
Department of Neuroinflammation, University College London, Institute of Neurology, 1 Wakefield Street, London WC1 N 1PK, UK. Electronic address: j.pocock@ucl.ac.uk.

Abstract

Neuroinflammation is a pathological hallmark of Alzheimer's disease (AD), and microglia, the brain's resident phagocyte, are pivotal for the immune response observed in AD. Microglia act as sentinel and protective cells, but may become inappropriately reactive in AD to drive neuropathology. Recent Genome Wide Association Studies (GWAS) have identified more than 20 gene variants associated with an increased risk of late-onset AD (LOAD), the most prevalent form of AD [1]. The findings strongly implicate genes related to the immune response (CR1, CD33, MS4A, CLU, ABCA7, EPHA1 and HLA-DRB5-HLA-DRB1), endocytosis (BIN1, PICALM, CD2AP, EPHA1 and SORL1) and lipid biology (CLU, ABCA7 and SORL1) [2-8], and many encode proteins which are highly expressed in microglia [1]. Furthermore, recent identification of a low frequency mutation in the gene encoding the triggering receptor expressed in myeloid cells 2 protein (TREM2) confers increased risk of AD in LOAD cohorts with an effect size similar to that for APOE, until recently the only identified genetic risk factor associated with LOAD [9,10(••)] (Figure 1). The present review summarises our current understanding of the probable roles of microglial genes in the regulation of neuroinflammatory processes in AD and their relation to other processes affecting the disease's progression.

PMID:
26517285
DOI:
10.1016/j.conb.2015.10.004
[Indexed for MEDLINE]

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