In addition, the toxicity of Aβ peptides has been most often studied outside the context and the crucial characteristics of AD, such as: (i) the very slow disease progression that requires several decades to cause discernable pathological manifestations; (ii) its link to advanced age and to the ε4 allele of apolipoprotein-E (APOE) gene, as major risk factors; and (iii) the selective and early degeneration of the central cholinergic neurons. Here, APOE is linked to Alzheimer disease.