Compounding Effects of APOE4 and Blood Neurodegenerative Biomarkers on Cognitive Decline in Community‐dwelling Older Adults

In a biracial cohort of community-dwelling older adults having three different serum neurodegenerative biomarkers and APOE4 carrier status simultaneously examined in the same study, we showed higher neurodegeneration (t-tau), axonal injuries (NfL), and reactive astrocytes and neuroinflammation (GFAP) accelerated cognitive decline in genetically susceptible APOE4 carriers. Hence, these findings highlight the detrimental role of APOE4 in exacerbating neurodegenerative processes, with not only significant implications for understanding and tracking the progression of neurodegenerative diseases, but also a call for inclusivity of APOE4 status in scientific investigations and in clinical trials.