Alzheimer’s disease (AD) is a neurodegenerative disorder characterized clinically by gradual and progressive memory loss and pathologically by the presence of senile plaques (Aβ deposits) and neurofibrillary tangles (NFTs, Tau deposits) in the brain [1]. AD has a substantial but heterogeneous genetic component. Mutations in the amyloid-beta precursor protein (APP) and Presenilin genes (PSEN1 and PSEN2) [2, 3] cause autosomal dominant AD (ADAD) which is typically associated with early-onset (< 65 years). In contrast, the most common manifestation of AD presents late-onset (LOAD) and accounts for the majority of the cases (90–95%). Despite appearing sporadic in nature, a complex genetic architecture underlies LOAD risk. APOE ε4 is the most common genetic risk factor, increasing the risk in three- to eightfold [4]. In addition, recent whole genome and whole exome analyses have identified rare coding variants in TREM2 [5, 6], PLD3 [7], ABCA7 [8, 9], and SORL1 [10, 11] that are associated with AD and confer risk comparable to that of carrying one APOE ε4 allele. Besides age at onset, the clinical presentations of LOAD and ADAD are remarkably similar with
