costs the health care system in the United States more than $200
billion annually (Alzheimer’s Association, 2015). As the population
ages, AD incidence is expected to rapidly increase (projected to be
13.8 million affected individuals in 2050), which will cause
tremendous suffering for affected individuals and their families,
and health care systems worldwide (costs are expected to exceed $1
trillion annually by 2050 [Alzheimer’s Association, 2015]).
AD can be classified as either early- or late-onset, with most of
(>99%) cases being late-onset. Early-onset AD is characterized by
autosomal dominant mutations in 1 of 3 genes (presenilin 1, presenilin
2, or amyloid precursor protein). The genetic architecture of
late-onset AD is more complex. To date, more than 20 distinct
genetic loci have been implicated in AD by genome-wide association
studies (GWAS) and linkage studies (Lambert et al., 2013), and
additional rare variants in several genes have been identified