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APOE4 by the numbers
The strongest common genetic risk factor for Alzheimer's, measured two ways: in one research cohort of 2,430 people, and across the 745 studies in the library that name it in their title. In the cohort, carrying APOE4 was a weaker predictor of MCI progression than every biochemical and imaging marker tested.
Sources. The cohort figures come from this site's aggregate analysis of the Alzheimer's Disease Neuroimaging Initiative, the same analysis behind From MCI to Alzheimer's. The library figures are counted when the page loads, from studies in our library whose title names APOE or apolipoprotein E and from the topic tags we give each study.
Figures are derived from ADNI data under a Data Use Agreement. Only aggregate statistics are published; no individual participant records are shown. This page is not endorsed by ADNI or the National Institute on Aging.
How common APOE4 is in the cohort
Share of genotyped ADNI participants carrying at least one APOE4 allele, by diagnosis at enrolment. The two groups had similar mean ages (72.8 and 73.3 years).
The gap between the two bars is the simplest statement of what APOE4 does. People who had already developed mild cognitive impairment were far more likely to carry the variant than people of the same age whose cognition was normal. That is a difference in who gets the condition. It says nothing yet about what happens to a carrier after diagnosis, which is the next question.
What APOE4 predicts once MCI is present
- 0.643AUC for conversion by 36 months, APOE4 carrier vs non-carrier (95% CI 0.607–0.680)
- 5 of 6rank among the single baseline markers tested
- 719MCI participants with genotype and follow-up
- 30.2%of all followed MCI participants converted by 36 months
| Marker | AUC | 95% CI | n |
|---|---|---|---|
| CSF Aβ42 | 0.739 | 0.694–0.784 | 484 |
| CSF p-tau181 | 0.732 | 0.685–0.779 | 484 |
| CSF total tau | 0.723 | 0.676–0.771 | 484 |
| Hippocampal volume / ICV | 0.685 | 0.621–0.748 | 266 |
| APOE4 carrier vs non-carrier | 0.643 | 0.607–0.680 | 719 |
| Age at baseline | 0.556 | 0.513–0.599 | 728 |
An AUC of 0.5 is chance and 1.0 is perfect separation. APOE4 status on its own, at 0.643, sits well above chance and well below the spinal-fluid markers and hippocampal volume. Interpretation: the gene raises the odds of having the Alzheimer's process, but once someone has MCI, measuring the process directly tells you more about the next three years than the gene does. The joint model on the conversion page makes the same point with all the markers together.
APOE in the research library
- 745studies with APOE in the title, of 27,380
- 1,619studies carrying an APOE auto-tag
- 715of the title matches are peer-reviewed
- 599published before 2025; 145 from 2025 on
Studies with APOE in the title, by year of publication, from 1990. The shaded band marks 2025 onward, where the library's recent collection rounds inflate every count; the shape before the band is the trend.
By subject
| Subject | Studies |
|---|---|
| Genetics | 460 |
| Biomarkers | 42 |
| Treatments | 27 |
| TREM2 and immune genetics | 24 |
| Risk factors | 23 |
| Tau biomarkers | 15 |
| Long-term cohort studies | 14 |
| Brain scans and imaging | 13 |
By study design
| Design group | Studies |
|---|---|
| No design recorded | 563 |
| Cohort or longitudinal study | 97 |
| Cross-sectional study | 26 |
| Randomised or phase 2/3 trial | 22 |
| Case-control study | 20 |
| Meta-analysis or systematic review | 17 |
The ten highest-scoring APOE studies, and what they report
Ranked by usefulness score. Where the record carries an effect size, it is quoted as stored, with no rounding or rewording.
- Alzheimer's blood-based biomarkers, incident dementia, and interactions with age, APOE status, and hormone therapy
- Lecanemab for treatment of individuals with early Alzheimer's Disease (AD) who are apolipoprotein E ε4 (ApoE ε4) non-carriers or heterozygotes
-
APOE Genotype and Alzheimer Disease Risk Across Age, Sex, and Population Ancestry
Effect as recorded: APOE ε3/ε4 vs ε3/ε3 odds ratio for AD: 4.54 East Asian, 3.46 White, 2.18 Black, 1.90 Hispanic
-
The ApoE Gene Is Related with Exceptional Longevity: A Systematic Review and Meta-Analysis
Effect as recorded: OR=0.18; OR=0.44; OR=0.48
-
Effect of the Apolipoprotein E Genotype on Cognitive Change During a Multidomain Lifestyle Intervention: A Subgroup Analysis of a Randomized Clinical Trial
Effect as recorded: 46.3%
- Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE
- Efficacy and APOE ε4-stratified risk of donanemab in Alzheimer's disease: A systematic review and meta-analysis of randomized clinical trials
- Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans
-
Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study
Effect as recorded: 3.3%
-
Sex Differences in Apolipoprotein E and Alzheimer Disease Pathology Across Ancestries
Effect as recorded: 52.8%; 2.6%; 1.1%
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Related: genetics in plain English · From MCI to Alzheimer's · what amyloid and tau do