Aβ aggregation as the cause of AD. A modified version of the amyloid cascade hypothesis is shown. This version takes into account the possibility that Aβ aggregates other than those found in classic amyloid deposits initiate the pathological cascade. It is possible that Aβ-induced toxicity in turn results in alterations in the brain, such as increased APP and apoE expression, that enhance Aβ deposition, although this is not shown in the figure. Besides known genetic pathways, a pathway in which normal Aβ levels in the context of normal aging may lead to Aβ accumulation is shown. “APPSw” refers to the APP Swedish mutant linked to familial AD; this mutation alters the lysine-methionine sequence immediately preceding Aβ to asparagine-leucine. Trisomy 21 is also known as Down syndrome.