title: Microglial dysfunction connects depression and Alzheimer's disease.
abstract: Alzheimer's disease (AD) and major depressive disorder (MDD) are highly prevalent neuropsychiatric conditions with intriguing epidemiological overlaps. Depressed patients are at increased risk of developing late-onset AD, and around one in four AD patients are co-diagnosed with MDD. Microglia are the main cellular effectors of innate immunity in the brain, and their activation is central to neuroinflammation - a ubiquitous process in brain pathology, thought to be a causal factor of both AD and MDD. Microglia serve several physiological functions, including roles in synaptic plasticity and neurogenesis, which may be disrupted in neuroinflammation. Following early work on the 'sickness behavior' of humans and other animals, microglia-derived inflammatory cytokines have been shown to produce depressive-like symptoms when administered exogenously or released in response to infection. MDD patients consistently show increased circulating levels of pro-inflammatory cytokines, and anti-inflammatory drugs show promise for treating depression. Activated microglia are abundant in the AD brain, and concentrate around senile plaques, hallmark lesions composed of aggregated amyloid-β peptide (Aβ). The Aβ burden in affected brains is regulated largely by microglial clearance, and the complex activation state of microglia may be crucial for AD progression. Intriguingly, recent reports have linked soluble Aβ oligomers, toxins that accumulate in AD brains and are thought to cause memory impairment, to increased brain cytokine production and depressive-like behavior in mice. Here, we review recent findings supporting the inflammatory hypotheses of AD and MDD, focusing on microglia as a common player and therapeutic target linking these devastating disorders.
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil.
authors.forename: Luís Eduardo
authors.initials: LE
authors.lastname: Santos
authors.affiliation: Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil.
authors.forename: Danielle
authors.initials: D
authors.lastname: Beckman
authors.affiliation: Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21944-590, Brazil. Electronic address: ferreira@bioqmed.ufrj.br.
authors.forename: Sergio T
authors.initials: ST
authors.lastname: Ferreira
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology*; D000818:Animals; D003863:Depression / Q000276:immunology*; D006801:Humans; D017628:Microglia / Q000276:immunology*
keywords: Alzheimer’s disease; Major depressive disorder; Microglia; Neuroinflammation