APOE and Alzheimer disease: On the other hand, APOE-ε4 has been identified as a strong AD genetic risk factor, with odds ratios of 1.78–9.93 across different studies or ethnic groups11–13, and has been reported to modulate brain amyloid-beta (Aβ) burden, tau protein level14,15, neuronal activity16,17, immune status18,19, blood–brain barrier integrity20 and longevity21,22.