Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
1993/08/13 by E. H. Corder, Elizabeth H. Corder, Ann M. Saunders +12 · 87 citations
Medicine · Neuroscience · #Alzheimer's disease research and treatments #Nuclear Receptors and Signaling #Cholinesterase and Neurodegenerative Diseases
paper · doi:10.1126/science.8346443
Abstract
The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.
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- Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. [europepmc]
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- Alzheimer's disease: the challenge of the second century. [europepmc]
- Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. [europepmc]
- Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy. [europepmc]
- Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease. [europepmc]
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- Alzheimer's disease risk genes and mechanisms of disease pathogenesis. [europepmc]
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- Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria. [europepmc]
- Microglia in Alzheimer's disease. [europepmc]
- Inflammation as a central mechanism in Alzheimer's disease. [europepmc]
- Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. [europepmc]
- Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies. [europepmc]
- Alzheimer Disease: An Update on Pathobiology and Treatment Strategies. [europepmc]
- APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline. [europepmc]
- The Amyloid-β Pathway in Alzheimer's Disease. [europepmc]
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