Neuroinflammation in Alzheimer's disease.

TitleNeuroinflammation in Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2015
AuthorsHeneka MT, Carson MJ, Khoury JEl, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K, Frautschy SA, Finsen B, Brown GC, Verkhratsky A, Yamanaka K, Koistinaho J, Latz E, Halle A, Petzold GC, Town T, Morgan D, Shinohara ML, V Perry H, Holmes C, Bazan NG, Brooks DJ, Hunot S, Joseph B, Deigendesch N, Garaschuk O, Boddeke E, Dinarello CA, Breitner JCS, Cole GM, Golenbock DT, Kummer MP
JournalLancet Neurol
Volume14
Issue4
Pagination388-405
Date Published2015 Apr
ISSN1474-4465
KeywordsAlzheimer Disease, Animals, Anti-Inflammatory Agents, Non-Steroidal, Astrocytes, Biomarkers, Brain Injuries, Clinical Trials as Topic, Disease Models, Animal, Disease Progression, Humans, Immunity, Innate, Immunization, Inflammation, Inflammation Mediators, Locus Coeruleus, Microglia, Nootropic Agents, Obesity, Phagocytosis, Protein Folding, Risk Factors, Severity of Illness Index
Abstract

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.

DOI10.1016/S1474-4422(15)70016-5
Alternate JournalLancet Neurol
PubMed ID25792098
Grant ListI01 BX001257 / BX / BLRD VA / United States
R01 AG021975 / AG / NIA NIH HHS / United States
R01 AT006816 / AT / NCCIH NIH HHS / United States
RC1 AG035878 / AG / NIA NIH HHS / United States

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