The Genetics of Alzheimer’s Disease and Parkinson’s Disease

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder. It is characterized by progressive loss of memory and other cognitive domains along with functional decline that can occur in the third to eighth decades. The early onset (<60 years old) familial forms of AD have an autosomal dominant inheritance linked to three causative genes: APP, PSEN1, and PSEN2. The most common sporadic form of AD occurs after the age of 60 and is associated with the APOE gene. The mechanistic contribution of these genes in AD pathogenesis has been studied extensively but is still unclear, suggesting that other AD associated genes remain to be elucidated. Parkinson's disease (PD) is the second most common neurodegenerative disorder. Idiopathic PD is the most frequent form of Parkinsonism, although rare forms of PD in which genetic factors dominate exist. Family studies have identified 13 causative genetic loci linked to PD of which 8 genes have been described: four autosomal dominant (SNCA, LRRK2, UCHL1, and HTRA2) and four autosomal recessive (PRKN, DJ1, PINK1, and ATP13A2). In addition, another gene has recently been described as a possible risk factor for PD (GBA). The function of these genes and their contribution to PD pathogenesis remains to be fully elucidated. Like AD, other genes that contribute to PD risk likely exist. The prevalence, incidence, clinical manifestations, and genetic components of these two neurodegenerative disorders, AD and PD, are discussed in this chapter. PU - SPRINGER PI - NEW YORK PA - 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES