GSK-3β is also involved in Aβ-induced toxicity throughdifferent mechanisms.89 Aβ is obtainedfrom a series of proteolytic cleavage of amyloid precursor protein(APP), a transmembrane protein highly expressed in the brain, whichundergoes two different metabolic pathways mediated by a group ofsecretases.90 The nonamyloidogenic pathwaymediated by α-secretase leads to fragments easily degraded,while the amyloidogenic pathway, mediated by BACE-1 and γ-secretasecomplex, leads to the formation of Aβ peptide which accumulatesin deposits in AD brain. The gene discussed is APP; the disease is Alzheimer disease.