Journal
NEUROBIOLOGY OF AGING
Volume 25, Issue 5, Pages 641-650Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2003.12.023
Keywords
ApoE genotype; AD risk; AD pathology
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Funding
- NIA NIH HHS [R01 AG20904, AG-NS-020-02, AG17824, P01 AG022074] Funding Source: Medline
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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 (epsilon2, epsilon3, epsilon4) 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 epsilon4 allele may account for 50% of AD in the United States. Further, the rarity of AD among carriers of the epsilon2 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. (C) 2004 Elsevier Inc. All rights reserved.
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