Microglia in dementia with Lewy bodies

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Microglial activation, or neuroinflammation, is often considered a cause of neurodegenerative diseases.
• However, the direct role of inflammation in α-synuclein pathology and neurofibrillary degeneration (NFD) remains debated.
• Dementia with Lewy bodies (DLB) is characterized by both α-synuclein pathology and NFD.

Purpose of the Study:

• To investigate the role of microglial activation and dystrophy in dementia with Lewy bodies (DLB).
• To compare microglial cell status in DLB cases versus non-demented (ND) controls.
• To determine if microglial dystrophy correlates with α-synuclein pathology or NFD severity.

Main Methods:

• Immunohistochemical analysis of microglial cells using iba1, anti-CD68, and anti-ferritin antibodies.
• Examination of temporal lobe and superior frontal gyrus tissue samples from five DLB cases and nine ND controls.
• Assessment of α-synuclein pathology, NFD (Braak staging), and microglial cell morphology (ramified vs. dystrophic).

Main Results:

• Activated microglia were largely absent in both DLB and ND cases, with only minor focal activation in controls.
• Both DLB and ND cases exhibited a mixture of ramified and dystrophic microglial cells, with no significant difference in dystrophic cell prevalence.
• Increased CD68 expression was observed in DLB cases compared to controls, potentially linked to lipofuscin deposits and impaired proteostasis.

Conclusions:

• Neurodegenerative changes in DLB are unlikely to stem directly from activated microglia.
• The findings suggest that dysfunctional microglia, rather than activated microglia, play a role in DLB.
• Increased CD68 expression in DLB may reflect impaired proteostasis rather than a direct inflammatory response to α-synuclein pathology.