Intriguingly, pathway analyses (Box 2) of AD implicate cholesterol metabolism and the innate immune response. 38 Genes attaining genome-wide significance point toward immune and inflammatory processes (CLU and CR1), lipid processing (APOE, CLU, and ABCA7), and endocytosis (PICALM, BIN1, CD2AP, and CD33). Altered immune function and lipid metabolism had previously been proposed as AD risk factors, but whether these represented causation or reverse causation was unclear. 39 The genetic findings now strongly point to the former.
