Evidence map›Paper›PMID 27209644›Full record

ReviewJournal of neuropathology and experimental neurology2016

"New Old Pathologies": AD, PART, and Cerebral Age-Related TDP-43 With Sclerosis (CARTS).

Peter T Nelson, John Q Trojanowski, Erin L Abner, Omar M Al-Janabi, Gregory A Jicha, Frederick A Schmitt, Charles D Smith, David W Fardo, Wang-Xia Wang, Richard J Kryscio and 5 more

Open access · bronzeAbstract readCase ReportsReview
In one paragraph

Review in Journal of neuropathology and experimental neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 1 pooled it
15.2field-weighted citation impact, top 1% 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

102 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Reframing TDP-43 in Alzheimer's disease: From co-pathology to neurovascular culprit.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  8. Review
  9. Primary age-related tauopathy.Acta neuropathologica · 2025
    Review
  10. Hippocampal tau distribution in primary age-related tauopathy: The Vantaa 85+ Study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  11. Article
  12. Genetic associations with dementia-related proteinopathy: Application of item response theory.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  13. Article
  14. Brain Banking in Dementia Studies.Methods in molecular biology (Clifton, N.J.) · 2024
    Review
  15. Article
  16. Article
  17. Prediction of neuropathologic lesions from clinical data.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
    Article
  18. Article
  19. Associations Between Loneliness and Cognitive Resilience to Neuropathology in Older Adults.The journals of gerontology. Series B, Psychological sciences and social sciences · 2023
    Article
  20. Article

42 more citing papers are in PubMed but not listed here.

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 3 institutions in 1 country.

Peter T NelsonFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC). pnels2@email.uky.edu.
John Q TrojanowskiFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
Erin L AbnerFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
Omar M Al-JanabiFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
Gregory A JichaFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
Frederick A SchmittFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
Charles D SmithFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
David W FardoFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
Wang-Xia WangFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
Richard J KryscioFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
Janna H NeltnerFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
Walter A KukullFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
Matthew D CykowskiFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
Linda J Van EldikFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
Eseosa T IghodaroFrom the Department of Pathology, Division of Neuropathology (PTN, JHN), Department of Neurology (GAJ, FAS, CDS), Department of Statistics (DWF, RJK), Department of Anatomy and Neurobiology (PTN, JHN, LJVE, ETI), Department of Epidemiology (ELA), and Sanders-Brown Center on Aging (PTN, ELA, OMA-J, GAJ, FAS, CDS, DWF, WXW, RJK, LJVE, ETI), University of Kentucky, Lexington, Kentucky; Department of Pathology & Laboratory Medicine and Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvannia (JQT); Department of Epidemiology, University of Washington, Seattle, Washington (WAK); and Department of Pathology, Houston Methodist Hospital, Houston, Texas (MDC).
University of Kentucky · USUniversity of Pennsylvania · USUniversity of Washington · US

Funding

RECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
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 DETRE, JOHN A · 1991 to 2020
$35.1M
University of Kentucky Alzheimer's Disease Core Center - Biomarker CoreP30AG028383 · NIA · UNIVERSITY OF KENTUCKY · PI GOLD, BRIAN TIMOTHY, VAN ELDIK, LINDA J · 2006 to 2020
$23.3M
Statistical Genetics Methods for Mixed PathologiesK25AG043546 · NIA · UNIVERSITY OF KENTUCKY · PI FARDO, DAVID WILLIAM · 2013 to 2015
$445k
Elucidating A Novel Mechanism for DementiaF30NS090714 · NINDS · UNIVERSITY OF KENTUCKY · PI IGHODARO, ESEOSA T. · 2016 to 2018
$73k
NIA NIH HHS K25 AG043546NIA NIH HHS P01 AG017586NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG028383NIA NIH HHS U01 AG016976NIA NIH HHS U19 AG010483NINDS NIH HHS F30 NS090714
6 · The paper itself

Abstract

The pathology-based classification of Alzheimer's disease (AD) and other neurodegenerative diseases is a work in progress that is important for both clinicians and basic scientists. Analyses of large autopsy series, biomarker studies, and genomics analyses have provided important insights about AD and shed light on previously unrecognized conditions, enabling a deeper understanding of neurodegenerative diseases in general. After demonstrating the importance of correct disease classification for AD and primary age-related tauopathy, we emphasize the public health impact of an underappreciated AD "mimic," which has been termed "hippocampal sclerosis of aging" or "hippocampal sclerosis dementia." This pathology affects >20% of individuals older than 85 years and is strongly associated with cognitive impairment. In this review, we provide an overview of current hypotheses about how genetic risk factors (GRN, TMEM106B, ABCC9, and KCNMB2), and other pathogenetic influences contribute to TDP-43 pathology and hippocampal sclerosis. Because hippocampal sclerosis of aging affects the "oldest-old" with arteriolosclerosis and TDP-43 pathologies that extend well beyond the hippocampus, more appropriate terminology for this disease is required. We recommend "cerebral age-related TDP-43 and sclerosis" (CARTS). A detailed case report is presented, which includes neuroimaging and longitudinal neurocognitive data. Finally, we suggest a neuropathology-based diagnostic rubric for CARTS.

Indexed as

DNA-Binding ProteinsAged, 80 and overAgingAlzheimer DiseaseAnimalsFemaleHippocampusHumansSclerosisTauopathiesDNA-Binding ProteinsTARDBP protein, humanArteriosclerosisCerebrovascular diseaseFrontotemporal lobar degenerationGenome-wide association studyNeurofibrillary tanglesPlaquesVCID.

Identifiers

PMID27209644
PMCPMC6366658
OpenAlexW2400971574

What OpenQuestion holds

Textmetadata
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.