title: Apolipoprotein E and central nervous system disorders: reviews of clinical findings.
abstract: Dementia is a major health problem in developed countries with over 25 million people affected worldwide and probably over 75 million people at risk during the next 20 years. Alzheimer's disease (AD) is the most frequent cause of dementia (50-70%), followed by vascular dementia (30-40%), and mixed dementia (15-20%). AD pathogenesis is still to be elucidated but it is believed to be the complex interaction between genetic and environmental factors in later life. Three causative genes for familial AD have been identified: amyloid precursor protein, presenilin-1, and presenilin-2. There are 150 genes involved with increased neuronal vulnerability to premature death in the AD brain. Among these susceptibility genes, the apolipoprotein E (ApoE) gene is the most prevalent as a risk for AD pathogenic process in which complex interactions between genetic and environmental factors are involved, leading to a cascade of pathogenic events converging in final pathways to premature neuronal death. Some of these mechanisms are common to several neurodegenerative disorders that differ depending upon the genes affected and the involvement of environmental conditions. ApoE is a key lipoprotein in lipid and cholesterol metabolism and it is also the major risk gene for AD and many other central nervous system disorders. The pathogenic role of ApoE-4 is still to be clarified; however, diverse evidence suggests that ApoE may play pleiotropic functions in dementia and central nervous system disorders.
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan. mtakeda@psy.med.osaka-u.ac.jp
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
authors.forename: Rocío
authors.initials: R
authors.lastname: Martínez
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Tanaka
authors.forename: Masayasu
authors.initials: M
authors.lastname: Okochi
authors.forename: Shinji
authors.initials: S
authors.lastname: Tagami
authors.forename: Takashi
authors.initials: T
authors.lastname: Morihara
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Ramón
authors.initials: R
authors.lastname: Cacabelos
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D002493:Central Nervous System Diseases / Q000235:genetics / Q000378:metabolism*; D015444:Exercise / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D016875:tau Proteins