Closing the sex/gender gap in dementia: homing in on the vasculature (biomarkers)

Abstract

AbstractAs we move toward precision medicine approaches, we cannot continue to pursue a one model fits all. Sex differences in brain aging and degeneration have been reported across the spectrum of research methodologies from human epidemiological studies and drug trials to model systems of degenerative brain disease. Blood proteomic biomarkers combined with clinical data can provide useful multi‐modal disease models in humans to uncover important biological associations with relevance to human disease. Small vessel disease in aging or AD is prevalent in the aging populations and represents a common and important risk factor for cognitive impairment. Dysregulated angiogenesis is emerging as a relevant pathology in SVD‐related vascular cognitive impairment with potential for therapeutic modulation. Recent work by our group and others is suggesting that the association of plasma markers of angiogenesis with clinical outcomes is sex dimorphic. Results demonstrate several age and sex‐dependent associations between groups of markers that capture both beneficial and pathological aspects of angiogenesis in aging. Much remains to be uncovered regarding underlying mechanisms, interactions with neurodegenerative pathologies, and ideal windows for sex‐informed therapeutic interventions on angiogenesis. However, the emerging body of work on sex differences regarding angiogenesis in aging, AD and other neurodegenerative disorders, represents a critical first step toward demonstrating the relevance of sex/gender to therapeutically oriented studies of vascular pathologies in dementia‐causing diseases.