Resting-state functional connectivity changes in aging apoE4 and apoE-KO mice.

Area of Science:

• Neuroscience
• Genetics
• Medical Imaging

Background:

• Apolipoprotein E (APOE) genotype is linked to neurodegenerative disease risk.
• APOE ε4 carriers exhibit altered brain functional connectivity (FC) compared to other isoforms.
• The underlying causes of reduced FC in APOE ε4 carriers are not fully understood.

Purpose of the Study:

• To investigate the relationship between APOE genotype, vascular function, synaptic repair, and brain FC.
• To determine if vascular and synaptic factors contribute to age-related FC decline in APOE ε4 carriers.

Main Methods:

• Utilized multimodal MRI techniques (perfusion, diffusion) and immunohistochemistry in apoE4 and apoE-knock-out (KO) mice.
• Assessed FC, perfusion, diffusion, and synaptic density in adult (12 months) and old (18 months) mice.
• Compared findings against wild-type controls.

Main Results:

• Both apoE4 and apoE-KO mice showed FC deficits compared to wild-type.
• In apoE4 mice, FC deficits correlated with hippocampal diffusivity; perfusion deficits and reduced synaptic density appeared later.
• In apoE-KO mice, FC deficits were associated with reduced brain perfusion from adulthood.

Conclusions:

• Evidence supports a link between APOE genotype and brain connectivity, potentially mediated by vascular factors and APOE's role in synaptic modulation.
• Multimodal MR neuroimaging effectively assesses brain function, early neuropathology, and aging effects in translational research.