Apoe ε4 allele
Apoe ε4 allele has been studied in 10 papers since 2016: 10 observational studies in people; 1 in the past year. The newest paper, Jul 1, 2026: “APOE-ε4 carriership and dementia risk over 10 years among Asian American and White older adults”.
10 papers study it19 findingsUpdated
“APOE-ε4 carriership was associated with higher dementia risk across groups”
1 of its findings points the other way.
- 8 independent labs in 7 countries
- 1 finding against
- Funders: National Institutes of Health and others
- 1 of 19 findings with company ties
- Humans10
What did studies of Apoe ε4 allele find?
16Studies of Apoe ε4 allele measured 16 outcomes; the most studied are gray matter volume (1 study), entorhinal cortex tau PET (1) and tau PET burden (1).
Gray matter volume
upin humans1downin humans1
1 study
Gray matter volume
upin humans1downin humans1
Apoe ε4 allele is linked with higher gray matter volume in humans.
“APOE-ε4 was also associated to greater GMv in the right thalamus, left occipital gyrus, and right frontal cortex.”
Humansright thalamus, left occipital gyrus, right frontal cortexn = 533
Alzheimer's & dementia : the journal of the Alzheimer's Association
Apoe ε4 allele is linked with lower gray matter volume in humans (additive effect with ε4 allele count).
“We found APOE-ε4 additive GMv reductions in the right hippocampus, caudate, precentral gyrus, and cerebellar crus.”
Humansadditive effect with ε4 allele countright hippocampus, caudate, precentral gyrus, cerebellar crusn = 533
Alzheimer's & dementia : the journal of the Alzheimer's Association
Entorhinal cortex tau PET
upin humans1
1 study
Entorhinal cortex tau PET
upin humans1
Apoe ε4 allele is linked with higher entorhinal cortex tau PET in humans after accounting for amyloid-β in mediation analysis.
“In mediation analyses, APOE-ε4 only retained an Aβ-independent effect on tau in the ERC.”
Humansafter accounting for amyloid-β in mediation analysisentorhinal cortexn = 462
European journal of nuclear medicine and molecular imaging
Tau PET burden
upin humans1
1 study
Tau PET burden
upin humans1
Apoe ε4 allele is linked with higher tau PET burden in humans (compared with APOE-ε3 homozygotes; across regional tau PET measures) (βstd range 0.27-0.51 across regional measures).
“APOE-ε4 participants showed higher Aβ (βstd [95%CI]: 0.64 [0.42, 0.82], p < 0.001) and tau burden”
Humanscompared with APOE-ε3 homozygotes; across regional tau PET measuresbrainn = 462
European journal of nuclear medicine and molecular imaging
Amyloid-β PET burden
upin humans1
1 study
Amyloid-β PET burden
upin humans1
Apoe ε4 allele is linked with higher amyloid-β PET burden in humans (compared with APOE-ε3 homozygotes) (βstd 0.64 (95% CI 0.42 to 0.82)).
“APOE-ε4 participants showed higher Aβ (βstd [95%CI]: 0.64 [0.42, 0.82], p < 0.001)”
Humanscompared with APOE-ε3 homozygotesbrainn = 462
European journal of nuclear medicine and molecular imaging
Cognitive function
no changein humans1
1 study
Cognitive function
no changein humans1
Apoe ε4 allele was not clearly linked with cognitive function in humans (heterozygotes compared with non-carriers, middle-aged and older adults).
“ɛ4 heterozygotes did not differ from non-carriers on any measure of objective or subjective cognition.”
Humansheterozygotes compared with non-carriers, middle-aged and older adultsɛ4 heterozygotes
Journal of Alzheimer's disease : JAD
Memory impairment
downin humans1
1 study
Memory impairment
downin humans1
Apoe ε4 allele is linked with worse memory impairment in humans (effect grew with age in pooled middle-aged HBP and older AIBL adults; homozygotes).
“The effect of ɛ4 homozygosity increases with older age.”
Humanseffect grew with age in pooled middle-aged HBP and older AIBL adults; homozygotesɛ4 homozygotes
Journal of Alzheimer's disease : JAD
Memory
downin humans1
1 study
Memory
downin humans1
Apoe ε4 allele is linked with worse memory in humans (homozygotes compared with heterozygotes and non-carriers, Healthy Brain Project).
“Greater memory impairment was observed in middle-aged ɛ4 homozygotes compared with ɛ4 heterozygotes and non-carriers.”
Humanshomozygotes compared with heterozygotes and non-carriers, Healthy Brain Projectɛ4 homozygotesn = 50
Journal of Alzheimer's disease : JAD
Where memory component retention
downin humans1
1 study
Where memory component retention
downin humans1
Apoe ε4 allele is linked with lower where memory component retention in humans (significant group-by-component-by-condition interaction).
“the presence of the ApoE ε4 allele resulted in a disproportionately detrimental effect on the where component retention in the verbal episodic memory task”
Humanssignificant group-by-component-by-condition interaction
Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists
Longitudinal cognitive decline in language, visual-spatial ability and processing speed
no changein humans1
1 study
Longitudinal cognitive decline in language, visual-spatial ability and processing speed
no changein humans1
Apoe ε4 allele was not clearly linked with longitudinal cognitive decline in language, visual-spatial ability and processing speed in humans.
“No significant APOE-ε4 effects were found for language, visual-spatial ability, or processing speed.”
Humans
Apolipoprotein E ε4 allele effects on longitudinal cognitive trajectories are sex and age dependent
Alzheimer's & dementia : the journal of the Alzheimer's Association
Longitudinal attention decline
upin humans1
1 study
Longitudinal attention decline
upin humans1
Apoe ε4 allele is linked with higher longitudinal attention decline in women; effect greater at older baseline age.
“In women, older baseline age was associated with greater APOE-ε4 effects on longitudinal decline in attention, detectible at baseline age of 66.”
Humansin women; effect greater at older baseline agefemalesn = 561
Apolipoprotein E ε4 allele effects on longitudinal cognitive trajectories are sex and age dependent
Alzheimer's & dementia : the journal of the Alzheimer's Association
All 16Fewer
What is Apoe ε4 allele linked with?
2Studies link Apoe ε4 allele with 2 measures, most often dementia (1 study) and stage N3 sleep duration (1).
Dementia
upin humans1
1 study
Dementia
upin humans1
Apoe ε4 allele is linked with a higher risk of dementia in humans (10-year risk ratios 1.59 to 1.96 across groups).
“APOE-ε4 carriership was associated with higher dementia risk across groups”
Humansacross Chinese, Japanese, Filipino and non-Latino White participants; pooled logistic regression10 years
APOE-ε4 carriership and dementia risk over 10 years among Asian American and White older adults
Alzheimer's & dementia : the journal of the Alzheimer's Association
Stage N3 sleep duration
upin humans1
1 study
Stage N3 sleep duration
upin humans1
Apoe ε4 allele is associated with stage N3 sleep duration in humans (two copies of the ε4 allele (ε4/ε4) compared with ε4 non-carriers) (62±5.2 minutes vs 40±0.8 minutes in non-carriers).
“Total time in stage N3 sleep was significantly higher (p<0.0001) among the 40 MrOS participants carrying two copies of the ε4 allele”
Humanstwo copies of the ε4 allele (ε4/ε4) compared with ε4 non-carriersmalesn = 40
APOEε4 and slow wave sleep in older adults
PloS one