title: Microglia in Alzheimer's disease: A multifaceted relationship.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder affecting elderly people worldwide, which is mainly characterized by cerebral amyloid-beta (Aβ) plaque deposition and neurofibrillary tangle formation. The interest in microglia arose from the overwhelming experimental evidence that outlined a key role of neuroinflammation in AD pathology. Microglia constitute the powerhouse of the innate immune system in the brain. It is now widely accepted that microglia are myeloid-derived cells that infiltrate the developing brain at the early embryonic stages, and acquire a highly ramified phenotype postnatally. Microglia use these dynamic ramifications as sentinels to sense and detect any occurring alteration in brain homeostasis. Once a danger signal is detected, microglia get activated by acquiring a less ramified phenotype, and mount adequate responses that range from phagocyting cell debris to secreting inflammatory and trophic factors. Earlier reports have demonstrated, unequivocally, that microglia surround Aβ plaques and internalize Aβ microaggregates. However, the implication of these observations in AD pathology, and consequently treatment, is still a matter of debate. Nonetheless, targeting the activity of these cells constituted a convergent point in this debate. Unfortunately, the conflicting experimental findings obtained following the modulation of microglial activity in AD, further fueled the debate. This review aims at providing an overview regarding what we know about the implication of microglia in AD pathology, and treatment. The emerging role of monocytes is also discussed.
authors.affiliation: Neuroscience Laboratory, CHU de Québec Research Center (CHUL), Department of Molecular Medicine, Faculty of Medicine, Laval University, Canada.
authors.forename: Ayman
authors.initials: A
authors.lastname: ElAli
authors.affiliation: Neuroscience Laboratory, CHU de Québec Research Center (CHUL), Department of Molecular Medicine, Faculty of Medicine, Laval University, Canada. Electronic address: serge.rivest@crchuq.ulaval.ca.
authors.forename: Serge
authors.initials: S
authors.lastname: Rivest
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology*; D000818:Animals; D006801:Humans; D017628:Microglia / Q000276:immunology*
keywords: Alzheimer’s disease; Cell signaling; Innate immunity; Microglia; Neuroinflammation; Phagocytosis