Abstract

Alzheimer’s disease (AD) is the most frequent cause of dementia, it manifests as a progressive decline in memory and other cognitive domains. The genetics of AD is complex and heterogeneous. Most cases are “sporadic late onset”, however, a small percentage of cases have an early onset and usually aggregate within families. Early studies revealed that a number of genes, including both rare mutations and common polymorphisms, play an important role in the development of AD. More recently it has been proposed that genetic variation may also explain some of the other features of clinical phenotype, such as age at onset, disease duration, cognitive decline, behavioral and psychiatric symptoms and so on. In this review, we compared the clinical phenotypes of reported mutations within the three causative genes and some common polymorphisms, with an emphasis on their heterogeneity. Hopefully, the unique phenotypic features of individual mutation will enable us to study molecular mechanisms, potentially explaining phenotypic differences and providing useful knowledge for the development of new therapeutic agents.

Keywords: Alzheimer’s disease; Genotype; Phenotype