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Rigshospitalet - a part of Copenhagen University Hospital
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APOE and dementia - resequencing and genotyping in 105,597 individuals

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INTRODUCTION: The mechanism behind the strong association between the ɛ2/ɛ3/ɛ4 apolipoprotein E gene (APOE) polymorphism and Alzheimer's disease is not well-characterized. Because low plasma levels of apoE associate with risk of dementia, genetic variants altering apoE levels in general may also associate with dementia.

METHODS: The APOE gene was sequenced in 10,369 individuals, and nine amino acid-changing variants with frequencies ≥2/10,000 were further genotyped in 95,228 individuals. Plasma apoE levels were measured directly.

RESULTS: Risk of all dementia and Alzheimer's disease (AD) increased with decreasing genetically determined apoE levels (P = 5 × 10-4 and P = 1 × 10-4 after APOE ɛ2/ɛ3/ɛ4 adjustment). Hazard ratios (95% confidence intervals) for all dementia and AD were 2.76 (1.39 to 5.47) and 4.92 (2.36 to 10.29) for the group with the genetically lowest apoE versus ɛ33.

DISCUSSION: We found that genetically low apoE levels increase and genetically high levels decrease risk, beyond ɛ2/ɛ3/ɛ4. This underscores that dementia risk more likely relates to variants affecting levels of apoE.

Original languageEnglish
JournalAlzheimer's & dementia : the journal of the Alzheimer's Association
Volume16
Issue number12
Pages (from-to)1624-1637
Number of pages14
ISSN1552-5260
DOIs
Publication statusPublished - Dec 2020

    Research areas

  • Alzheimer's disease, APOE, apolipoprotein E, dementia, genetics, rare variation

ID: 61972804