Evidence map›Paper›PMID 38520065›Full record

ArticleAging cell2024

Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4-induced brain pathology.

Brendan Miller, Su-Jeong Kim, Kevin Cao, Hemal H Mehta, Neehar Thumaty, Hiroshi Kumagai, Tomomitsu Iida, Cassandra McGill, Christian J Pike, Kamila Nurmakova and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
6.1field-weighted citation impact, top 3% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Article
  3. Genetic analysis of neurodegenerative diseases.The Journal of clinical investigation · 2026
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Observational
  9. Article
  10. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 2 countries.

Brendan MillerLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.ORCID 0000-0002-7461-7973
Su-Jeong KimLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Kevin CaoLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Hemal H MehtaLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Neehar ThumatyLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Hiroshi KumagaiLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Tomomitsu IidaLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Cassandra McGillLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Christian J PikeLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Kamila NurmakovaDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
Zachary A LevineDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
Patrick M SullivanDepartment of Medicine (Geriatrics), Duke University Medical Center, Durham, North Carolina, USA.
Kelvin YenLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Nilüfer Ertekin-TanerDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.ORCID 0000-0003-4436-8889
Gil AtzmonDepartment of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
Nir BarzilaiDepartment of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
Pinchas CohenLeonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
University of Southern California · USAlbert Einstein College of Medicine · USYale University · USDuke University · USJacksonville College · US

Funding

Peripheral and Central Biomarkers of Alzheimer's Disease in Diverse CohortsU19AG074879 · NIA · MAYO CLINIC JACKSONVILLE · PI Minerva Maria Carrasquillo · 2023 to 2026
$42.0M
RESEARCH TRAINING IN GERONTOLOGYT32AG000037 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JENNIFER A AILSHIRE, EILEEN M CRIMMINS · 1985 to 2026
$13.2M
The Role of the Glucose-regulated Protein GRP78/BiP in Stress Resistance and AginP01AG034906 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LONGO, VALTER D. · 2011 to 2016
$9.3M
USC-Buck Institute Nathan Shock Admin CoreP30AG068345 · NIA · BUCK INSTITUTE FOR RESEARCH ON AGING · PI LITHGOW, GORDON J · 2020 to 2024
$5.0M
Molecular Networks Underlying Resilience to Alzheimer's Disease Among APOE E4 CarriersR01AG057912 · NIA · YALE UNIVERSITY · PI GAITERI, CHRISTOPHER A., HIGGINS-CHEN, ALBERT TZONGYANG · 2017 to 2021
$4.5M
Sex differences in the relationship between APOE and AD: Role of sexual differentiationRF1AG058068 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GATZ, MARGARET, LADU, MARY JO · 2017 to 2017
$3.8M
Ethnic-specific Effects of Mitochondrial DNA Variants and Environmental Factors on Cognitive Functioning and DementiaR01AG068405 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI COHEN, PINCHAS, CRIMMINS, EILEEN M · 2020 to 2024
$3.6M
Humanin is an AD resilience factor through its interaction with APOE4RF1AG061834 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI COHEN, PINCHAS · 2018 to 2018
$3.3M
Metformin-Regulated Mitochondrial Peptides and their Effects on AgingR01AG069698 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI COHEN, PINCHAS · 2020 to 2024
$2.1M
National Institute on Aging - National Institutes of Health (NIH) AG057912National Institute on Aging - National Institutes of Health (NIH) P01AG034906National Institute on Aging - National Institutes of Health (NIH) P30AG068345National Institute on Aging - National Institutes of Health (NIH) R01AG061834National Institute on Aging - National Institutes of Health (NIH) R01AG068405National Institute on Aging - National Institutes of Health (NIH) R01AG069698National Institute on Aging - National Institutes of Health (NIH) T32AG00037NIA NIH HHS P01 AG034906NIA NIH HHS P30 AG068345NIA NIH HHS R01 AG057912NIA NIH HHS R01 AG068405NIA NIH HHS R01 AG069698NIA NIH HHS RF1 AG058068NIA NIH HHS RF1 AG061834NIA NIH HHS T32 AG000037NIA NIH HHS U19 AG074879NIH HHS RF1AG058068
6 · The paper itself

Abstract

The APOE4 allele is recognized as a significant genetic risk factor to Alzheimer's disease (AD) and influences longevity. Nonetheless, some APOE4 carriers exhibit resistance to AD even in advanced age. Humanin, a mitochondrial-derived peptide comprising 24 amino acids, has variants linked to cognitive resilience and longevity. Our research uncovered a unique humanin variant, P3S, specifically enriched in centenarians with the APOE4 allele. Through in silico analyses and subsequent experimental validation, we demonstrated a strong affinity between humanin P3S and APOE4. Utilizing an APOE4-centric mouse model of amyloidosis (APP/PS1/APOE4), we observed that humanin P3S significantly attenuated brain amyloid-beta accumulation compared to the wild-type humanin. Transcriptomic assessments of mice treated with humanin P3S highlighted its potential mechanism involving the enhancement of amyloid beta phagocytosis. Additionally, in vitro studies corroborated humanin P3S's efficacy in promoting amyloid-beta clearance. Notably, in the temporal cortex of APOE4 carriers, humanin expression is correlated with genes associated with phagocytosis. Our findings suggest a role of the rare humanin variant P3S, especially prevalent among individuals of Ashkenazi descent, in mitigating amyloid beta pathology and facilitating phagocytosis in APOE4-linked amyloidosis, underscoring its significance in longevity and cognitive health among APOE4 carriers.

Indexed as

Apolipoprotein E4BrainLongevityAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAnimalsApolipoproteins EDisease Models, AnimalFemaleHeterozygoteHumansIntracellular Signaling Peptides and ProteinsMaleMiceMice, TransgenicAmyloid beta-PeptidesApoE protein, humanApolipoprotein E4Apolipoproteins EhumaninIntracellular Signaling Peptides and ProteinsAlzheimer's diseasehumaninlongevitymicroproteinmitochondrial DNA variationsmall open reading frame

Identifiers

PMID38520065
PMCPMC11258485
OpenAlexW4393116582

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.