ABSTRACT
References 455
The genetic architecture of Alzheimer’s disease (AD) remains elusive despite the success in identifying patients with rare autosomal dominant early-onset Alzheimer’s disease (EOAD). Mutations in three genes, the amyloid protein precursor (APP) and the presenilin genes (PS1 and PS2) located on chromosomes 21, 14 and 1, respectively, exert their effect in a fully penetrant manner. The gene that encodes apolipoprotein E (ApoE) is the only genetic variant which consistently influences disease risk. Contrastingly, susceptibility for late-onset Alzheimer’s disease (LOAD) shows a less obvious familial aggregation and is therefore likely to be governed by a number of risk alleles located on a number of different genes. Continued research in this complex area of the genes and proteins involved in AD will help establish a logical basis for therapeutics and management.
