title: Psychosocial stress on neuroinflammation and cognitive dysfunctions in Alzheimer's disease: the emerging role for microglia?
abstract: Chronic psychosocial stress is increasingly recognized as a risk factor for late-onset Alzheimer's disease (LOAD) and associated cognitive deficits. Chronic stress also primes microglia and induces inflammatory responses in the adult brain, thereby compromising synapse-supportive roles of microglia and deteriorating cognitive functions during aging. Substantial evidence demonstrates that failure of microglia to clear abnormally accumulating amyloid-beta (Aβ) peptide contributes to neuroinflammation and neurodegeneration in AD. Moreover, genome-wide association studies have linked variants in several immune genes, such as TREM2 and CD33, the expression of which in the brain is restricted to microglia, with cognitive dysfunctions in LOAD. Thus, inflammation-promoting chronic stress may create a vicious cycle of aggravated microglial dysfunction accompanied by increased Aβ accumulation, collectively exacerbating neurodegeneration. Surprisingly, however, little is known about whether and how chronic stress contributes to microglia-mediated neuroinflammation that may underlie cognitive impairments in AD. This review aims to summarize the currently available clinical and preclinical data and outline potential molecular mechanisms linking stress, microglia and neurodegeneration, to foster future research in this field.
authors.affiliation: Neuroscience Center, HiLIFE, University of Helsinki, Viikinkaari 4, FIN-00014, Helsinki, Finland.
authors.forename: Sami
authors.initials: S
authors.lastname: Piirainen
authors.affiliation: Neuroscience Center, HiLIFE, University of Helsinki, Viikinkaari 4, FIN-00014, Helsinki, Finland.
authors.forename: Andrew
authors.initials: A
authors.lastname: Youssef
authors.affiliation: Research Institute of Marine Drugs and Nutrition, Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; Department of Psychology and Neuroscience, Dalhousie University, 1355 Oxford St, Life Sciences Centre, Halifax, Nova Scotia B3H4R2, Canada.
authors.forename: Cai
authors.initials: C
authors.lastname: Song
authors.affiliation: Research Institute of Marine Drugs and Nutrition, Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; Institute of Translational Biomedicine, St Petersburg State University, St Petersburg 199034, Russia; Ural Federal University, Ekaterinburg 620002, Russia; ZENEREI Research Center, Slidell, LA 70458, USA.
authors.forename: Allan V
authors.initials: AV
authors.lastname: Kalueff
authors.affiliation: Department of Neurosciences, Alzheimer Research Laboratory, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Landreth
authors.affiliation: A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 70150, Kuopio, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Malm
authors.affiliation: Neuroscience Center, HiLIFE, University of Helsinki, Viikinkaari 4, FIN-00014, Helsinki, Finland; Zhejiang University-University of Edinburgh Joint Institute, 718 East Haizhou Rd., Haining, Zhejiang 314400, China; Psychiatry Research Centre, Beijing Huilongguan Hospital, Peking University, Beijing 100096, China. Electronic address: li.tian@helsinki.fi.
authors.forename: Li
authors.initials: L
authors.lastname: Tian
mesh_terms: D000544:Alzheimer Disease; D060825:Cognitive Dysfunction; D055106:Genome-Wide Association Study; D006801:Humans; D017628:Microglia; D013315:Stress, Psychological
keywords: Amyloid clearance; Dementia; Late-onset Alzheimer's disease; Microglia; Psychosocial stress