Reduced levels of angiogenesis biomarkers predict increased symptom severity in Chinese Americans with Alzheimer's disease with demographic-specific effect

Abstract

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 (p = 0.045) as well as memory performance (p = 0.006), and that this relationship was most pronounced in AD (biomarker composite score within AD vs MMSE & memory, both p < 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.

Keywords: Alzheimer’s disease; Chinese American; angiogenesis; plasma biomarkers; vascular disease.