Bidirectional relationship between functional connectivity and amyloid-β deposition in mouse brain

Area of Science:

• Neuroscience
• Alzheimer's Disease Research
• Aging

Background:

• Alzheimer's disease (AD) is characterized by amyloid plaques.
• Reduced functional connectivity is observed in AD patients, aging individuals, and those with amyloid burden.
• Previous studies noted a spatial correlation between functional connectivity and Aβ deposition in humans.

Purpose of the Study:

• To investigate the relationship between Aβ deposition, normal aging, and functional connectivity in a mouse model.
• To explore whether functional connectivity predicts Aβ deposition vulnerability.

Main Methods:

• Utilized functional connectivity optical intrinsic signal (fcOIS) imaging in APP/PS1 transgenic mice and age-matched controls.
• Quantified Aβ deposition and measured bilateral functional connectivity across brain regions.
• Examined functional connectivity in young and aged mice, both before and after Aβ plaque formation.

Main Results:

• Aβ deposition significantly reduced bilateral functional connectivity in older APP/PS1 mice.
• The extent of Aβ deposition correlated with the degree of local, age-related functional connectivity decline.
• Normal aging alone reduced functional connectivity in the retrosplenial cortex.
• In young APP/PS1 mice, regional functional correlation predicted later Aβ deposition in older mice.

Conclusions:

• Both Aβ deposition and normal aging contribute to region-specific disruptions in brain functional connectivity.
• Baseline functional connectivity may predict a brain region's vulnerability to subsequent amyloid-β plaque accumulation.
• Findings provide a mouse model framework for studying the interplay of aging, Aβ, and functional connectivity in AD.