AD has multifactorial etiology and is thought to result from many inter-related components, including genetic and environmental factors.
AD is classified according to the age of the person at onset – late-onset (≥65 years; most common form of AD) and early-onset (≤65 years of age).[Jiang et al., 2013] AD can be further classified into familial AD (FAD), which follows a genetically determined inheritance pattern, or sporadic AD, where there is no obvious inheritance pattern.1,4 Familial aggregation (i.e., two or more family members with the disease) is a putative risk for AD.[Winblad et al., 2016] Cases of early-onset familial AD (EOFAD) are now known to be caused by specific mutations in genes located on different chromosomes.2 Examples of modified genes are: the amyloid precursor protein (APP) gene on chromosome 21, the presenilin 1 (PSEN1) gene on chromosome 14, and the presenilin 2 (PSEN2) gene on chromosome 1.2
Genetics are also implicated in the development of sporadic late-onset AD. Natural variations (alleles) of the apolipoprotein E (ApoE) gene, on chromosome 19, influence the susceptibility of an individual to AD.3,4 The ApoE gene has three common alleles – ApoE 2, 3 and 4.[Bendlin et al., 2010] There is an increased risk of developing AD, and at an earlier age of disease onset, in people carrying one or two copies of the ApoE 4 allele.3 However, the ApoE 4 allele does not determine who will develop AD.1 The ApoE 2 allele shows a moderately protective effect against AD.1 Other susceptibility genes include CR1 (complement component receptor 1), PICALM (phosphatidylinositol-binding clathrin assembly protein), CLU (clusterin), TREM2 (triggering receptor expressed on myeloid cells 2), and TOMM40 (translocase of outer mitochondrial membrane 40 homologue).4
Environmental factors can also be implicated in the development of AD. These include exposure to certain chemicals, the presence of pre-existing medical conditions, and individual lifestyle factors.2 These environmental factors are discussed on the following slides.