APOE and Alzheimer disease: The APOE4 genotype in AD is associated with accelerated Aβ aggregation, impaired Aβ clearance and an earlier age of AD onset due to insufficient uptake and clearance of Aβ through the LRP1 receptor on microglia and perivascular astrocytes [17], leading to deficiency in both intracellular proteolysis and glymphatic clearance of Aβ.