Evidence map›Paper›PMID 40615639›Full record

ArticleGeroScience2026

Increased genetic protection against Alzheimer's disease in centenarians.

Harold Bae, Zeyuan Song, Amanat Ali, Takashi Sasaki, Niccolò Tesi, Hannah Lords, Anastasia Leshchyk, Yukiko Abe, Nobuyoshi Hirose, Yasumichi Arai and 14 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00707694 (Searching for Longevity Genes in the Historically Unique Ashkenazi Jewish Population), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00707694 recruitingnot on this map

Searching for Longevity Genes in the Historically Unique Ashkenazi Jewish Population

TypeobservationalSponsorAlbert Einstein College of MedicineRan1998 to 2032Enrolled2,000ConditionsExtreme Longevity
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Linguistic features from paragraph recall are markers of cognitive impairment.Journal of the International Neuropsychological Society : JINS · 2026
    Article
  2. Utility of Polygenic Risk Scores in Families with Exceptional Longevity.medRxiv : the preprint server for health sciences · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Harold BaeSchool of Nutrition and Public Health, College of Health, Oregon State University, Corvallis, OR, USA. harold.bae@oregonstate.edu.ORCID 0000-0003-2219-3969
Zeyuan SongInstitute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA.
Amanat AliDepartment of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
Takashi SasakiCenter for Supercentenarian Medical Research, Keio University School of Medicine, Tokyo, Japan.
Niccolò TesiDelft Bioinformatics Lab, Delft University of Technology, Mekelweg 2, 2628CD, Delft, The Netherlands.
Hannah LordsDivision of Computational Biomedicine, Boston University, Boston, MA, USA.
Anastasia LeshchykDivision of Computational Biomedicine, Boston University, Boston, MA, USA.
Yukiko AbeCenter for Supercentenarian Medical Research, Keio University School of Medicine, Tokyo, Japan.
Nobuyoshi HiroseCenter of Supercentenarian Medical Research, School of Medicine, Keio University, Tokyo, Japan.
Yasumichi AraiCenter for Supercentenarian Medical Research, Keio University School of Medicine, Tokyo, Japan.
Nir BarzilaiDepartment of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
Erica F WeissInstitute for Aging Researchand the Einstein-NSC, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
Marc HulsmanSection Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam, UMC, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
Sven van der LeeSection Genomics of Neurodegenerative Diseases and Aging, Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam, UMC, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
Natasja M van SchoorDepartment of Epidemiology and Data Sciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
Martijn HuismanDepartment of Epidemiology and Data Sciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
Yolande PijnenburgAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, UMC, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
Wiesje van der FlierAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, UMC, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands.
Marcel ReindersDelft Bioinformatics Lab, Delft University of Technology, Mekelweg 2, 2628CD, Delft, The Netherlands.
Henne HolstegeDelft Bioinformatics Lab, Delft University of Technology, Mekelweg 2, 2628CD, Delft, The Netherlands.
Sofiya MilmanDepartment of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.
Thomas T PerlsBoston University, Avedisian School of Medicine, Chobanian &, Boston, MA, USA.
Stacy L AndersenBoston University, Avedisian School of Medicine, Chobanian &, Boston, MA, USA.
Paola SebastianiInstitute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA.

Funding

NIH HHS R01-AG061844NIH HHS U19-AG023122NIH HHS U19-AG063893NIH HHS UH2/UH3 AG064704
6 · The paper itself

Abstract

We constructed a polygenic protective score specific to Alzheimer's disease (AD PPS) based on the current literature among the participants enrolled in five studies of healthy aging and extreme longevity in the USA, Europe, and Asia. This AD PPS did not include variants on apolipoprotein E (APOE) gene. Comparisons of AD PPS in different data sets of healthy agers and centenarians showed that centenarians have stronger genetic protection against AD compared to individuals without familial longevity. The current study also shows evidence that this genetic protection increases with increasingly older ages in centenarians (centenarians who died before reaching age 105 years, semi-supercentenarians who reached age 105 to 109 years, and supercentenarians who reached age 110 years and older). However, the genetic protection was of modest size: the average increase in AD PPS was approximately one additional protective allele per 5 years of gained lifetime. Additionally, we show that the higher AD PPS was associated with better cognitive function and decreased mortality. Taken together, this analysis suggests that individuals who achieve the most extreme ages, on average, have the greatest protection against AD. This finding is robust to different genetic backgrounds with important implications for universal applicability of therapeutics that target this AD PPS.

Indexed as

Alzheimer DiseaseLongevityAged, 80 and overApolipoproteins EFemaleGenetic Predisposition to DiseaseHumansMaleMultifactorial InheritanceUnited StatesApolipoproteins EAlzheimer’s diseaseCentenariansCognitive functionExtreme longevityPolygenic risk score

Identifiers

PMID40615639
PMCPMC12972374

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.