Biomarkers

Area of Science:

• Neuroimaging
• Machine Learning in Medicine
• Alzheimer's Disease Research

Background:

• Investigated sex differences in the SPARE-AD (Signature for the Progression of Alzheimer’s Disease) imaging signature.
• Examined the relationship between SPARE-AD, age, APOE ε4 allele, and multi-organ biological age gap (BAG).

Purpose of the Study:

• To determine sex-specific patterns in brain atrophy signatures related to Alzheimer's disease.
• To assess the influence of genetic factors (APOE ε4) and biological age on these signatures.

Main Methods:

• Utilized data from 53,622 cognitively normal participants from the iSTAGING and MULTI consortia.
• Employed a support vector machine (SPARE-AD model) to quantify brain atrophy.
• Applied generalized linear models and ANCOVA to analyze sex differences, BAG associations, and APOE ε4 effects.

Main Results:

• SPARE-AD scores increased with age and were positively associated with the number of APOE ε4 alleles.
• Sex differences in SPARE-AD were observed, with higher scores in women at younger ages and in men at older ages.
• The brain BAG showed the strongest association with SPARE-AD, followed by other BAGs significant in men but not women.

Conclusions:

• SPARE-AD demonstrates age- and sex-dependent trajectories, highlighting differential aging patterns in the brain.
• The APOE ε4 allele influences SPARE-AD, particularly in men, suggesting sex-specific genetic effects on neurodegeneration.
• Biological age, especially brain age, is a critical factor associated with brain atrophy signatures indicative of Alzheimer's disease risk.