title: ApoE genotype accounts for the vast majority of AD risk and AD pathology.
abstract: In this review, evidence is provided that apolipoprotein E (apoE) genotype accounts for the majority of Alzheimer's disease (AD) risk and pathology. The three major human isoforms, apoE2, apoE3, and apoE4, are encoded by different alleles (2, 3, 4) and regulate lipid metabolism and redistribution. ApoE isoforms differ in their effects on AD risk and pathology. Clinical and epidemiological data have indicated that the 4 allele may account for 50% of AD in the United States. Further, the rarity of AD among carriers of the 2 allele suggests that allelic variations in the gene encoding this protein may account for over 95% of AD cases. ApoE4 disrupts memory function in rodents. Further studies have indicated that fragments of apoE may contribute to both plaque and tangle formation. Thus, the epidemiologic and basic science evidence suggest that apoE genotype accounts for the vast majority of AD risk and pathology.
authors.affiliation: Departments of Behavioral Neuroscience and Neurology, L470, ONPRC, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201, USA. raberj@ohsu.edu
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
authors.forename: Yadong
authors.initials: Y
authors.lastname: Huang
authors.forename: J Wesson
authors.initials: JW
authors.lastname: Ashford
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D000818:Animals; D001057:Apolipoproteins E / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008569:Memory Disorders / Q000209:etiology / Q000235:genetics; D016874:Neurofibrillary Tangles / Q000235:genetics; D058225:Plaque, Amyloid / Q000235:genetics; D012306:Risk; D012737:Sex Factors
chemical_list: D001057:Apolipoproteins E