Disrupted Brain Structural Connectivity: Pathological Interactions Between Genetic APOE ε4 Status and Developed MCI...

Area of Science:

• Neuroscience
• Genetics
• Gerontology

Background:

• Alzheimer's disease (AD) is a neurodegenerative disorder with significant genetic and age-related risk factors.
• The apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for AD.
• Mild cognitive impairment (MCI) is an intermediate stage between normal aging and AD, also associated with increased AD risk.

Purpose of the Study:

• To investigate the interaction between the APOE ε4 allele and MCI in a Chinese Han population.
• To identify potential synergistic effects that could serve as biomarkers for early AD detection and intervention.

Main Methods:

• Neuropsychological tests and APOE genotyping were performed on 885 Han Chinese subjects (≥55 years).
• Structural and diffusion tensor MRI scans were acquired for 110 participants.
• Subjects were categorized into four groups: ε4+ MCI, ε4+ normal cognition (NC), ε4- MCI, and ε4- NC.

Main Results:

• Significant interactions between APOE ε4 and MCI were observed in general cognitive function (p=0.001) and white matter network connectivity (p<0.05).
• The combination of APOE ε4 positivity and MCI was associated with reduced Mini-Mental Status Examination (MMSE) scores.
• This combination also showed decreased global white matter network connectivity and right hippocampus (rHIP) nodal efficiency.

Conclusions:

• The co-occurrence of APOE ε4 and MCI exacerbates cognitive decline and disrupts brain network integrity.
• These interacting factors represent promising targets for developing sensitive biomarkers for early AD diagnosis.
• Findings support the utility of combined genetic and cognitive assessments in clinical trials for early-stage AD.