Lewy body dementia
Summary
Lewy body dementia (LBD) encompasses dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), characterized by cognitive fluctuations, visual hallucinations, parkinsonism, and REM sleep behavior disorder. Alpha-synuclein Lewy body pathology and amyloid co-pathology are common features. Neuroinflammation driven by microglia accompanies Lewy body accumulation.
Microglial Relevance
Microglial activation is a consistent finding in LBD cortex and subcortical regions. Alpha-synuclein activates microglia through TLR2 and NLRP3 inflammasome pathways, triggering proinflammatory cytokine release. APOE4 is a risk factor for DLB and may impair microglial clearance of alpha-synuclein. TREM2 variants have been linked to increased LBD risk. CSF biomarkers of microglial activation (including sTREM2 and GFAP) are elevated in LBD. The overlap between AD and LBD pathologies creates shared and distinct microglial biology.
Sources
- Microglial activation in Lewy body dementia (2018)
Last reviewed: June 1, 2026