Evidence map›Paper›PMID 37815677›Full record

ArticleActa neuropathologica2023

Histopathologic brain age estimation via multiple instance learning.

Gabriel A Marx, Justin Kauffman, Andrew T McKenzie, Daniel G Koenigsberg, Cory T McMillan, Susan Morgello, Esma Karlovich, Ricardo Insausti, Timothy E Richardson, Jamie M Walker and 8 more

Open access · hybridAbstract read
In one paragraph

Article in Acta neuropathologica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.3field-weighted citation impact, top 9% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Digital neuropathology of neurodegenerative disorders: Foundations, research advances, and future directions.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  4. Primary age-related tauopathy.Acta neuropathologica · 2025
    Review
  5. Article
  6. Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  7. Decoding pathology: the role of computational pathology in research and diagnostics.Pflugers Archiv : European journal of physiology · 2025
    Review
  8. Article
  9. Neurodegeneration: 2024 update.Free neuropathology · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 2 countries.

Gabriel A MarxDepartment of Pathology, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, 1 Gustave L. Levy Place, Box 1194, New York, NY, 10029, USA.
Justin KauffmanDepartment of Pathology, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, 1 Gustave L. Levy Place, Box 1194, New York, NY, 10029, USA.
Andrew T McKenzieDepartment of Pathology, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, 1 Gustave L. Levy Place, Box 1194, New York, NY, 10029, USA.
Daniel G KoenigsbergDepartment of Pathology, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, 1 Gustave L. Levy Place, Box 1194, New York, NY, 10029, USA.
Cory T McMillanFrontotemporal Degeneration Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Susan MorgelloDepartment of Pathology, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, 1 Gustave L. Levy Place, Box 1194, New York, NY, 10029, USA.
Esma KarlovichDepartment of Pathology, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, 1 Gustave L. Levy Place, Box 1194, New York, NY, 10029, USA.
Ricardo InsaustiHuman Neuroanatomy Laboratory, School of Medicine, University of Castilla-La Mancha, Albacete, Spain.
Timothy E RichardsonDepartment of Pathology, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, 1 Gustave L. Levy Place, Box 1194, New York, NY, 10029, USA.
Jamie M WalkerDepartment of Pathology, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, 1 Gustave L. Levy Place, Box 1194, New York, NY, 10029, USA.
Charles L WhiteDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Bergan M BabrowiczDepartment of Pathology, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, 1 Gustave L. Levy Place, Box 1194, New York, NY, 10029, USA.
Li ShenNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, New York, NY, USA.
Ann C McKeeDepartment of Pathology, Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA.
Thor D SteinDepartment of Pathology, Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA.
PART Working Group
Kurt FarrellDepartment of Pathology, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, 1 Gustave L. Levy Place, Box 1194, New York, NY, 10029, USA. kurt.farrell@mssm.edu.
John F CraryDepartment of Pathology, Icahn School of Medicine at Mount Sinai, Friedman Brain Institute, 1 Gustave L. Levy Place, Box 1194, New York, NY, 10029, USA. john.crary@mountsinai.org.ORCID 0000-0002-0556-293X
Allen Institute for Brain Science · USBoston University · USThe University of Texas Southwestern Medical Center · USUniversity of Castilla-La Mancha · ESUniversity of Pennsylvania · US

Funding

Research Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI John Fonda Crary · 2020 to 2026
$31.0M
RL5: Research Education CoreP30AG072978 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Ann C. McKee · 2021 to 2026
$25.6M
Research Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DAVID A WOLK · 2021 to 2026
$24.8M
The Manhattan HIV Brain BankU24MH100931 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI MORGELLO, SUSAN · 2013 to 2023
$14.0M
Clinical Pathological Study of Cognitive Impairment in Essential TremorR01NS086736 · NINDS · YALE UNIVERSITY · PI COSENTINO, STEPHANIE ANN, LOUIS, ELAN D · 2014 to 2023
$8.1M
The Contribution of Age-Related Taupahtoies to Alzheimer's Disease-SupplementR01AG062348 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI CRARY, JOHN FONDA, DICKSON, DENNIS WILLIAM · 2018 to 2022
$4.5M
Age-related Tauopathy in HIV-associated Neurocognitive DisordersRF1AG060961 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CRARY, JOHN FONDA, MORGELLO, SUSAN · 2018 to 2018
$4.2M
Regulation of tau expression in Alzheimer disease and agingR01AG054008 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CRARY, JOHN FONDA · 2016 to 2020
$4.0M
The Contribution of Age-Related Tauopathies to Alzheimer's DiseaseRF1AG062348 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI John Fonda Crary, DENNIS WILLIAM DICKSON · 2023 to 2026
$4.0M
Mechanisms of Age-Related TauopathyR01NS095252 · NINDS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI John Fonda Crary · 2015 to 2026
$3.4M
Mechanisms of age-related tauopathyRF1NS095252 · NINDS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CRARY, JOHN FONDA · 2022 to 2022
$2.5M
Metabolic Signatures for Alzheimer's DiseaseR01NS054008 · NINDS · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F · 2007 to 2009
$921k
NIA NIH HHS K01 AG070326NIA NIH HHS K01AG070326NIA NIH HHS P30 AG066514NIA NIH HHS P30AG066514NIA NIH HHS P30 AG072978NIA NIH HHS P30 AG072979NIA NIH HHS R01 AG054008NIA NIH HHS R01AG060961NIA NIH HHS R01 AG062348NIA NIH HHS R01AG062348NIA NIH HHS RF1 AG060961NIA NIH HHS RF1 AG062348NIMH NIH HHS U24 MH100931NIMH NIH HHS U24MH100931NINDS NIH HHS R01AG054008NINDS NIH HHS R01 NS086736NINDS NIH HHS R01NS086736NINDS NIH HHS R01 NS095252NINDS NIH HHS R01NS095252NINDS NIH HHS RF1 NS095252
6 · The paper itself

Abstract

Understanding age acceleration, the discordance between biological and chronological age, in the brain can reveal mechanistic insights into normal physiology as well as elucidate pathological determinants of age-related functional decline and identify early disease changes in the context of Alzheimer's and other disorders. Histopathological whole slide images provide a wealth of pathologic data on the cellular level that can be leveraged to build deep learning models to assess age acceleration. Here, we used a collection of digitized human post-mortem hippocampal sections to develop a histological brain age estimation model. Our model predicted brain age within a mean absolute error of 5.45 ± 0.22 years, with attention weights corresponding to neuroanatomical regions vulnerable to age-related changes. We found that histopathologic brain age acceleration had significant associations with clinical and pathologic outcomes that were not found with epigenetic based measures. Our results indicate that histopathologic brain age is a powerful, independent metric for understanding factors that contribute to brain aging.

Indexed as

AgingBrainAccelerationAutopsyChild, PreschoolDNA MethylationEpigenesis, GeneticEpigenomicsHumansAgingBiological clockDigital pathologyMachine learningMethylation

Identifiers

PMID37815677
PMCPMC10627911
OpenAlexW4387472254

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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.