Review Article The Genetics of Alzheimer’s Disease

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Alzheimer’s disease is a progressive, neurodegenerative disease that represents a growing global health crisis. Two major forms of the disease exist: early onset (familial) and late onset (sporadic). Early onset Alzheimer’s is rare, accounting for less than 5 % of disease burden. It is inherited inMendelian dominant fashion and is caused bymutations in three genes (APP, PSEN1, and PSEN2). Late onset Alzheimer’s is common among individuals over 65 years of age. Heritability of this form of the disease is high (79%), but the etiology is driven by a combination of genetic and environmental factors. A large number of genes have been implicated in the development of late onset Alzheimer’s. Examples that have been con�rmed by multiple studies include ABCA7, APOE, BIN1, CD2AP, CD33, CLU, CR1, EPHA1,MS4A4A/MS4A4E/MS4A6E, PICALM, and SORL1. Despite tremendous progress over the past three decades, roughly half of the heritability for the late onset of the disease remains unidenti�ed. �inding the remaining genetic factors that contribute to the development of late onset Alzheimer’s disease holds the potential to provide novel targets for treatment and prevention, leading to the development of effective strategies to combat this devastating disease. 1