Evidence map›Paper›PMID 28877758›Full record

ArticleActa neuropathologica communications2017

Neuron loss and degeneration in the progression of TDP-43 in frontotemporal lobar degeneration.

Ahmed Yousef, John L Robinson, David J Irwin, Matthew D Byrne, Linda K Kwong, Edward B Lee, Yan Xu, Sharon X Xie, Lior Rennert, EunRan Suh and 4 more

Open access · goldAbstract read
In one paragraph

Article in Acta neuropathologica communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

30 citing papers in PubMed, 58 citations in OpenAlex.

  1. Aberrant Splicing Signatures Underpin Oligodendrocyte Damage in ALS and Neuron Loss in FTD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. Article
  3. Development of [Nature communications · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. New Approaches to the Treatment of Frontotemporal Dementia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Conserved gene signatures shared amongFrontiers in molecular biosciences · 2023
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

14 authors at 2 institutions in 1 country.

Ahmed YousefCenter for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
John L RobinsonCenter for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
David J IrwinCenter for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Matthew D ByrneCenter for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Linda K KwongCenter for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Edward B LeeCenter for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Yan XuCenter for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Sharon X XieDepartment of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Lior RennertDepartment of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
EunRan SuhCenter for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Vivianna M Van DeerlinCenter for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Murray GrossmanCenter for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Virginia M-Y LeeCenter for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
John Q TrojanowskiCenter for Neurodegenerative Disease Research and Institute on Aging, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. trojanow@upenn.edu.
University of Pennsylvania · USInstitute on Aging · US

Funding

Transgenic Mouse Models of Tau PathologiesP01AG017586 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LEE, VIRGINIA M · 2000 to 2021
$37.3M
UPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI XIE, SHARON XIANGWEN · 1991 to 2020
$35.1M
Epigenetic Editing of Mutant C9orf72R01NS095793 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI LEE, EDWARD BYUNG-HA · 2016 to 2020
$2.2M
Molecular neuropathology of TDP-43 proteinopathiesR21NS097749 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI LEE, EDWARD BYUNG-HA · 2016 to 2017
$443k
NIA NIH HHS P01 AG017586NIA NIH HHS P30 AG010124NINDS NIH HHS R01 NS095793NINDS NIH HHS R21 NS097749
6 · The paper itself

Abstract

Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is associated with the accumulation of pathological neuronal and glial intracytoplasmic inclusions as well as accompanying neuron loss. We explored if cortical neurons detected by NeuN decreased with increasing TDP-43 inclusion pathology in the postmortem brains of 63 patients with sporadic and familial FTLD-TDP. Semi-automated quantitative algorithms to quantify histology in tissue sections stained with antibodies specific for pathological or phosphorylated TDP-43 (pTDP-43) and NeuN were developed and validated in affected (cerebral cortex) and minimally affected (cerebellar cortex) brain regions of FTLD-TDP cases. Immunohistochemistry (IHC) for NeuN and other neuronal markers found numerous neurons lacking reactivity, suggesting NeuN may reflect neuron health rather than neuron loss in FTLD. We found three patterns of NeuN and pTDP-43 reactivity in our sample of cortical tissue representing three intracortical region-specific stages of FTLD-TDP progression: Group 1 showed low levels of pathological pTDP-43 and high levels NeuN, while Group 2 showed increased levels of pTDP-43, and Group 3 tissues were characterized by reduced staining for both pTDP-43 and NeuN. Comparison of non-C9orf72/GRN FTLD-TDP with cases linked to both GRN mutations and C9orf72 expansions showed a significantly increased frequency of Group 3 histopathology in the latter cases, suggesting more advanced cortical disease. Hence, we propose that IHC profiles of pTDP-43 and NeuN reflect the burden of pTDP-43 and its deleterious effects on neuron health.

Indexed as

AgedAlgorithmsAntigens, NuclearBrainC9orf72 ProteinCell DeathCohort StudiesDisease ProgressionDNA-Binding ProteinsFemaleFrontotemporal Lobar DegenerationGenetic Predisposition to DiseaseHumansImage Processing, Computer-AssistedImmunohistochemistryInclusion BodiesAntigens, NuclearC9orf72 ProteinC9orf72 protein, humanDNA-Binding ProteinsGRN protein, humanIntercellular Signaling Peptides and ProteinsNerve Tissue Proteinsneuronal nuclear antigen NeuN, humanProgranulinsTARDBP protein, humanC9orf72Frontotemporal lobar degenerationGRNNeuNNeurodegenerationTDP-43

Identifiers

PMID28877758
PMCPMC5586052
OpenAlexW2751125459

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.