Quantitative microglia morphological features correlate with diffusion MRI in 2-month-old 3xTg-AD mice

Area of Science:

• Neuroscience
• Neuroinflammation
• Neurodegenerative Diseases

Background:

• Microglia (MØ) are key players in brain homeostasis, with morphology reflecting function.
• Neuroinflammation's role in early Alzheimer's Disease (AD) pathogenesis is not fully understood.
• Previous work showed diffusion MRI (dMRI) detects early myelin abnormalities in 3xTg-AD mice.

Purpose of the Study:

• To quantitatively assess microglia (MØ) morphology in young 3xTg-AD mice.
• To investigate the association between MØ morphology and dMRI metrics.
• To understand the early role of MØ-mediated inflammation in AD pathogenesis.

Main Methods:

• Comparative analysis of MØ morphology in 2-month-old 3xTg-AD (TG) mice and age-matched normal control (NC) mice.
• Quantification of MØ cell number, size, and complexity.
• Correlation analysis between MØ morphological characteristics and diffusion MRI (dMRI) metrics (e.g., FA, KFA, radial diffusivity, axial diffusivity).

Main Results:

• TG mice exhibited significantly higher MØ numbers, with smaller and more complex cells compared to NC mice.
• Reduced myelin basic protein was observed in TG mice, particularly in the fimbria and cortex.
• MØ morphology correlated with dMRI metrics, indicating associations with myelin dysfunction and altered microstructural integrity.

Conclusions:

• Microglia (MØ) proliferation and activation are prevalent in young (2-month-old) 3xTg-AD mice.
• Diffusion MRI (dMRI) measures are sensitive to early microglial alterations in this AD model.
• These MØ changes are linked to myelin dysfunction and microstructural abnormalities, suggesting an early role in AD pathogenesis.