Microglia in Alzheimer's disease represent the brain's innate immune cells that play a dual role in AD pathogenesis — both promoting neuroinflammation that drives neurodegeneration and attempting to clear toxic amyloid deposits. Understanding microglial function is critical for developing disease-modifying therapies for Alzheimer's disease. [@microglia2020]
Overview
Microglia are the resident macrophage cells of the central nervous system (CNS), originating from yolk sac progenitors during embryonic development. In Alzheimer's disease, microglia become persistently activated in response to amyloid-beta (Aβ) plaques and neurofibrillary tangles, adopting a disease-associated microglia (DAM) phenotype. [@diseaseassociated2020]
Key aspects of microglial involvement in AD:
Amyloid clearance: Attempting to phagocytose and clear Aβ deposits
Neuroinflammation: Producing pro-inflammatory cytokines that contribute to neuronal damage
Plaque maintenance: Forming a protective barrier around amyloid plaques
Synaptic pruning: Eliminating synapses in an aberrant manner
Trophic support: Attempting to provide neurotrophic factors to neurons
Microglia in Alzheimer's disease represent the brain's innate immune cells that play a dual role in AD pathogenesis — both promoting neuroinflammation that drives neurodegeneration and attempting to clear toxic amyloid deposits. Understanding microglial function is critical for developing disease-modifying therapies for Alzheimer's disease. [@microglia2020]
Overview
Microglia are the resident macrophage cells of the central nervous system (CNS), originating from yolk sac progenitors during embryonic development. In Alzheimer's disease, microglia become persistently activated in response to amyloid-beta (Aβ) plaques and neurofibrillary tangles, adopting a disease-associated microglia (DAM) phenotype. [@diseaseassociated2020]
Key aspects of microglial involvement in AD:
Amyloid clearance: Attempting to phagocytose and clear Aβ deposits
Neuroinflammation: Producing pro-inflammatory cytokines that contribute to neuronal damage
Plaque maintenance: Forming a protective barrier around amyloid plaques
Synaptic pruning: Eliminating synapses in an aberrant manner
Trophic support: Attempting to provide neurotrophic factors to neurons
Molecular Biology
Pattern Recognition Receptors
Microglia recognize Aβ through multiple pattern recognition receptors: [@microglial2019]
TLRs (Toll-like receptors):
TLR2: Recognizes Aβ fibrils
TLR4: Activated by Aβ
TLR6: Co-receptor with TLR2
Scavenger receptors:
SR-A1: Class A scavenger receptor
CD36: Forms complex with TLR4/TLR6
RAGE: Receptor for advanced glycation end products