Evidence map›Paper›PMID 31929165›Full record

ArticleJournal of Alzheimer's disease : JAD2020

Effect Modifiers of TDP-43-Associated Hippocampal Atrophy Rates in Patients with Alzheimer's Disease Neuropathological Changes.

Marina Buciuc, Alexandra M Wennberg, Stephen D Weigand, Melissa E Murray, Matthew L Senjem, Anthony J Spychalla, Bradley F Boeve, David S Knopman, Clifford R Jack, Kejal Kantarci and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 13% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Pooled it
  2. Brain morphometry patterns in the presence of Alzheimer's disease and/or LATE neuropathologic changes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  17. Hippocampal sclerosis of aging at post-mortem is evident on MRI more than a decade prior.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
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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

15 authors at 2 institutions in 1 country.

Marina BuciucDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Alexandra M WennbergDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Stephen D WeigandDepartment of Health Science Research, Mayo Clinic, Rochester, MN, USA.
Melissa E MurrayDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Matthew L SenjemDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Anthony J SpychallaDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Bradley F BoeveDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
David S KnopmanDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Clifford R JackDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Kejal KantarciDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Joseph E ParisiDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Jennifer L WhitwellDepartment of Radiology, Mayo Clinic, Rochester, MN, USA.
Keith A JosephsDepartment of Neurology, Mayo Clinic, Rochester, MN, USA.
Mayo Clinic in Arizona · USMayo Clinic in Florida · US

Funding

SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9M
Research Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI NILUFER ERTEKIN-TANER · 2019 to 2026
$33.5M
Disease pathways in the population determined by amyloid, tau, and neurodegeneration imaging biomarkersR37AG011378 · NIA · MAYO CLINIC ROCHESTER · PI CLIFFORD R. JACK · 2018 to 2026
$6.8M
Understanding the role of TDP-43 in Alzheimers disease and FTLDR01AG037491 · NIA · MAYO CLINIC ROCHESTER · PI JOSEPHS, KEITH A · 2010 to 2024
$6.5M
Validating the New Criteria for Preclinical Alzheimer's diseaseR01AG041851 · NIA · MAYO CLINIC ROCHESTER · PI JACK, CLIFFORD R., KNOPMAN, DAVID S · 2012 to 2021
$6.3M
NIA NIH HHS P30 AG062677NIA NIH HHS P50 AG016574NIA NIH HHS R01 AG037491NIA NIH HHS R01 AG041851NIA NIH HHS R37 AG011378NIA NIH HHS U01 AG006786
6 · The paper itself

Abstract

backgroundTransactive response DNA-binding protein of 43 kDa (TDP-43) is associated with hippocampal atrophy in Alzheimer's disease (AD), but whether the association is modified by other factors is unknown.

objectiveTo evaluate whether the associations between TDP-43 and hippocampal volume and atrophy rate are affected by age, gender, apolipoprotein E (APOE) ɛ4, Lewy bodies (LBs), amyloid-β (Aβ), or Braak neurofibrillary tangle (NFT) stage.

methodsIn this longitudinal neuroimaging-clinicopathological study of 468 cases with AD neuropathological changes (Aβ-positive) that had completed antemortem head MRI, we investigated how age, gender, APOEɛ4, presence of LBs, Aβ, TDP-43, and Braak NFT stages are associated with hippocampal volumes and rates of atrophy over time. We included field strength in the models since our cohort included 1.5T and 3T scans. We then determined whether the associations between hippocampal atrophy and TDP-43 are modified by these factors using mixed effects models.

resultsOlder age, female gender, APOEɛ4, higher field strength, higher TDP-43, and Braak NFT stages were associated with smaller hippocampi. Rate of atrophy was greater with higher TDP-43 and Braak NFT stage, but lower in older patients. The association of TDP-43 with greater rate of atrophy was enhanced in APOEɛ4 carriers (p = 0.04).

conclusionNeurodegenerative effects of TDP-43 seem to be independent of most factors except perhaps APOE in cases with AD neuropathological changes. TDP-43 and tau appear to behave independently of one another.

Indexed as

AgedAged, 80 and overAge FactorsAlzheimer DiseaseAmyloid beta-PeptidesApolipoproteins EAtrophyAutopsyCohort StudiesDisease ProgressionDNA-Binding ProteinsFemaleHippocampusHumansLewy BodiesLongitudinal StudiesAmyloid beta-PeptidesApolipoproteins EDNA-Binding ProteinsTARDBP protein, humanAlzheimer’s diseaseapolipoprotein E4atrophydementiahippocampusMRIpathologyTDP-43

Identifiers

PMID31929165
PMCPMC7081101
OpenAlexW2999737624

What OpenQuestion holds

Textmetadata
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Registered trials

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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.