The factors that cause some individuals to depart from the relatively benign process of normal brain aging and instead undergo the pathological cascade that leads to AD are unknown. A number of genetic risk factors for AD have been proposed [9], [10], [11], [12], however only the apolipoprotein E (APOE) ε4-allele, which lowers the age of onset and accelerates the cognitive decline, has a large effect [13], [14]. Pathologically AD is characterized by the presence of two insoluble protein aggregates, senile plaques formed from the peptide β-amyloid (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein [15]. In rare familial AD, the cause of disease is autosomal dominant mutations in Aβ precursor protein (APP) or the Aβ-producing enzymes presenilins (PSEN1 or PSEN2), which are all thought to lead to increased levels of aggregated Aβ [9], [10], [16]. Likewise, mutations in tau (MAPT) that predispose it to aggregation can cause specific diseases that involve profound neurodegeneration and dementia [17], [18]. Thus, like in other neurodegenerative diseases such as Huntington's disease (HD) and Parkinson's disease, the formation of toxic insoluble aggregates seems
