We recently reported significant Aβ(1–40) and Aβ(1–42) levels in the guanidine-extractable, plaque-associated fraction in autopsy AD brain samples27 and we now reveal sex-dependent differences (with some influence of APOE ε4 status) in levels of soluble Aβ peptides in these same samples. The gene discussed is APOE; the disease is Alzheimer disease.