ApoE genotype accounts for the vast majority of AD risk and AD pathology

Jacob Raber, Yadong Huang, J. Wesson Ashford

Research output: Contribution to journalArticlepeer-review

476 Scopus citations

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 (ε2, ε3, ε4) 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 ε4 allele may account for 50% of AD in the United States. Further, the rarity of AD among carriers of the ε2 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.

Original languageEnglish (US)
Pages (from-to)641-650
Number of pages10
JournalNeurobiology of Aging
Volume25
Issue number5
DOIs
StatePublished - 2004

Keywords

  • AD pathology
  • AD risk
  • ApoE genotype

ASJC Scopus subject areas

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Aging
  • General Neuroscience
  • Developmental Biology

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