Microglial burden, activation and dystrophy patterns in frontotemporal lobar degeneration

Area of Science:

• Neuroscience
• Neuropathology
• Immunology

Background:

• Microglial dysfunction is linked to frontotemporal lobar degeneration (FTLD).
• While microglial changes are known in Alzheimer's disease (AD), they are less understood in FTLD.
• This study investigates microglial burden, activation, and dystrophy in FTLD, AD, and controls.

Purpose of the Study:

• To examine regional patterns of microglial burden, activation, and dystrophy in sporadic and genetic FTLD, AD, and control brains.
• To compare microglial characteristics across different FTLD subtypes (FTLD-tau, FTLD-TDP, FTLD-FUS) and genetic forms.
• To analyze microglial differences between grey and white matter within each disease group.

Main Methods:

• Immunohistochemistry using markers for phagocytic (CD68), antigen-presenting (CR3/43), and general microglia (Iba1).
• Quantitative assessment of microglial burden and activation (morphology).
• Semi-quantitative and qualitative assessment of microglial dystrophy, rod-shaped, and hypertrophic morphology in frontal and temporal grey and white matter.

Main Results:

• FTLD and AD cases showed higher microglial burden than controls, with often unchanged activation.
• Microglial burden was higher in white matter, while activation was greater in grey matter.
• Microglial dystrophy was more severe in FTLD and AD, particularly in white matter and in FTLD linked to GRN mutations; regional variations and subtype-specific morphologies were observed.

Conclusions:

• Microglial involvement in FTLD is regionally variable and linked to specific disease mechanisms.
• Findings support further research into microglial dysfunction in FTLD models.
• Consideration of anti-senescence therapies for FTLD is warranted.