APOE and Alzheimer disease: This positive association has been observed in both cognitively normal individuals and those diagnosed with AD.2, , , –6 Specifically, KL-VS heterozygosity (KL-VSHET) appears to mitigate age- and APOE ε4-related accumulation of Aβ42, T-tau, and P-tau, suggesting a potential protective role against AD pathology in APOE ε4 carriers.6, , , , , –12 In addition, recent findings indicate that KL-VSHET may also be associated with reduced age-related neuroinflammatory and neurodegenerative profiles in cognitively unimpaired adults at risk for AD.13