Stronger evidence that aggregates do trigger neurodegeneration (the so-called amyloid hypothesis) and are not just a consequence of the neurodegeneration, is provided by mutations in the gene for the amyloid beta precursor protein (APP) present in some human patients with AD (Selkoe, 1991; Hardy and Higgins, 1992; Hardy and Selkoe, 2002; Lansbury and Lashuel, 2006). This evidence concerns the gene APP and Alzheimer disease.