Apolipoprotein E (APOE) ε4 moderates the relationship between c-reactive protein, cognitive functioning, and white...

Area of Science:

• Neuroscience
• Inflammation Research
• Genetics

Background:

• C-reactive protein (CRP) and APOE ε4 allele are known risk factors for cognitive decline in older adults.
• The combined effects of CRP and APOE ε4 on cognitive and neurological function in younger and middle-aged adults remain understudied.

Purpose of the Study:

• To investigate the unique and cumulative effects of elevated CRP and APOE ε4 allele on cognitive function and white matter integrity in a cohort of post-9/11 war veterans.
• To determine if APOE ε4 carriers are more susceptible to the negative impacts of systemic inflammation on brain health.

Main Methods:

• Utilized data from 329 post-9/11 war veterans, including neuropsychological assessments, MRI scans, and APOE genotyping.
• Employed hierarchical linear regression and diffusion tensor imaging (DTI) with tract-based spatial statistics to analyze cognitive performance and white matter microstructure.

Main Results:

• A significant interaction between CRP and APOE ε4 was associated with poorer global cognition, executive functioning, and global fractional anisotropy.
• Elevated CRP levels were linked to diminished cognitive abilities and white matter integrity specifically in APOE ε4 carriers.
• Tract-based spatial statistics identified specific white matter tracts, including the corpus callosum and corona radiata, affected by the CRP × APOE ε4 interaction.

Conclusions:

• APOE ε4 carriers exhibit heightened vulnerability to the detrimental effects of systemic inflammation on cognitive function and white matter integrity.
• This interaction highlights a critical period for early intervention in individuals with the APOE ε4 allele to mitigate neuroinflammation-related risks.