Genotype and phenotype in Alzheimer's disease

Background Patients with Alzheimer's disease show a wide variation in clinical phenotype. Genetic research has been largely concerned with the role of mutations or common variants as risk factors for the disease, Do genetic factors also influence clinical phenotype? Aims To examine the evidence that genetic factors influence the clinical expression of the disease in addition to influencing risk. Method A selective review was made of the key literature, Results Mutations in three genes, coding for amyloid precursor protein, presenilin-1 and presenilin-2, and a common variation (epsilon4) in another gene, APOE, have been shown to iead to an earlier development ofthe disease, More recently, genetic association and twin studies have suggested a role for genetic factors in the development of other aspects of clinical phenotype, notably the appearance of non-cognitive symptoms. Conclusions In Alzheimer's disease genetic variation influences a number of aspects of clinical phenotype. Declaration of interest None.