Reduced Levels of Angiogenesis Biomarkers Predict Increased Symptom Severity in Chinese Americans with Alzheimer's Disease with Demographic-specific Effect

Alzheimer's disease (AD) symptomatology, while classically studied through the lens of amyloid-β and tau burden, is likely also influenced by multiple-interacting co-pathologies like vascular disease and dysmetabolism. These co-pathologies, especially vascular disease, occur disparately in the Chinese-American population and are often treatable via therapeutics and lifestyle modifications. Given this, we explored whether plasma biomarkers, including an array of vascular-related proteins, associate with cognition in a cohort of 34 Chinese Americans clinically diagnosed as cognitively normal, with mild cognitive impairment, or with AD. We found that a composite score of plasma angiogenesis biomarkers (MMP-1, bFGF, VEGF, and VEGF-C) were positively associated with total Mini Mental State Examination scores ( = 0.045) as well as memory performance ( = 0.006), and that this relationship was most pronounced in AD (biomarker composite score within AD vs MMSE & memory, both  < 0.001). To explore whether these findings were specific to the Chinese-American population, we repeated the above analyses in 73 demographically matched non-Hispanic White American participants and found no significant associations between angiogenesis biomarkers and MMSE or memory, highlighting the potential relevance of vascular dysregulation in Chinese Americans at risk for AD.