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61/100

✓ Peer-reviewed alzhub usefulness score 61 out of 100. Prevention and risk

Topic: Amyloid, tau and blood-test diagnosis

Plain-language summary

Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer's dementia, while the APOE2 allele is associated with a lower risk of Alzheimer's dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer's dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer's dementia cases and controls. APOE2/2 was associated with a low Alzheimer's dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls. Finding and targeting the factors by which APOE and its variants influence Alzheimer's disease could have a major impact on the understanding, treatment and prevention of the disease.

What this study adds

Evidence grade: Low

In this neuropathological study of more than 5,000 cases and controls, the APOE2/2 genotype was associated with a low odds ratio for Alzheimer's dementia compared with APOE2/3 and 3/3, and an exceptionally low odds ratio compared with APOE4/4. The authors suggest that finding and targeting the factors by which APOE and its variants influence Alzheimer's disease could have a major impact on understanding, treatment and prevention.

Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Reiman, E. M., Arboleda-Velasquez, J. F., Quiroz, Y. T., Huentelman, M. J., Beach, T. G., Caselli, R. J., et al. (2020). Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nature communications. https://doi.org/10.1038/s41467-019-14279-8

Vancouver

Reiman EM, Arboleda-Velasquez JF, Quiroz YT, Huentelman MJ, Beach TG, Caselli RJ, et al. Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nature communications. 2020. doi:10.1038/s41467-019-14279-8. PMID: 32015339.

BibTeX

@article{reiman2020-32015339,
  author  = {Reiman, E. M. and Arboleda-Velasquez, J. F. and Quiroz, Y. T. and Huentelman, M. J. and Beach, T. G. and Caselli, R. J. and Chen, Y. and Su, Y. and others},
  title   = {{Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study}},
  journal = {Nature communications},
  year    = {2020},
  doi     = {10.1038/s41467-019-14279-8},
  pmid    = {32015339},
  url     = {https://doi.org/10.1038/s41467-019-14279-8}
}

Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.

How to read this study

Design: our record does not state a study design, so check the methods section of the original before weighing the result.
Size: the record gives no participant count. Look for one in the original before trusting a pattern.
Effect: the record gives no effect size, so the summary above cannot say how large any difference was.

What the evidence grade means here

This page is graded low. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Low means the abstract matched neither pattern. It is the default label, and it does not mean the work is poor; many sound lab and imaging papers land here. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer's dementia, while the APOE2 allele is associated with a lower risk of Alzheimer's dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk.
APOE2/2 was associated with a low Alzheimer's dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls.

Why it matters

New to this subject? Start with our plain-English guide: Prevention →

Study details

Evidence strengthLow

How this study scored 61/100

Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.

Component	Points	Why
Journal tier	9 / 10	Tier 2 — leading specialty journal (Nature communications)
Journal's citation record	4 / 4	Nature Communications: journal h-index 747 (OpenAlex, 2026-10-29)
Study design	0 / 12	No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
Strength of evidence	1 / 5	Rated “low” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	2 / 5	2020 — within 10 year(s) of the newest study here
Sample size	0 / 4	Participant count not stated — scores zero (not stated in the record — scored 0)
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	0 / 3	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	6 / 7	Cited 480 times (OpenAlex, 2026-10-10)
Citations per year	5 / 5	60.0 citations a year over 8 year(s) since 2020
Impact for its field and year	5 / 6	Cited 32.1× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	4 / 6	Cited by 33 other studies in this library
Still being cited	4 / 4	Cited 226 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	1 / 4	Last-listed author Ryan M. Huebinger: h-index 19 (OpenAlex, whole career)
Institution's track record	3 / 3	University of Washington: institution h-index 3,540 (OpenAlex)
Multicenter collaboration	3 / 3	OpenAlex lists 61 institution(s) in 2 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 32015339)
Free to read	2 / 2	Free to read
Total	61 / 100	—

What each of these 20 components measures, and what this score is not →

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