Evidence map›Paper›PMID 40293530›Full record

ArticleActa neuropathologica2025

LATE-NC Stage 3: a diagnostic rubric to differentiate severe LATE-NC from FTLD-TDP.

Ryan K Shahidehpour, Yuriko Katsumata, Dennis W Dickson, Nikhil B Ghayal, Khine Zin Aung, Xian Wu, Panhavuth Phe, Gregory A Jicha, Allison M Neltner, Jessalin R C Archer and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Phenotypic diversity of frontotemporal lobar degeneration in two novel GRN variants from Colombia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  5. Article
  6. Article
  7. 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.

Ryan K ShahidehpourSanders-Brown Center On Aging, University of Kentucky, Rm 575 Lee Todd Jr Bldg/U. Kentucky, 789 S. Limestone Ave, Lexington, KY, 40536, USA.
Yuriko KatsumataSanders-Brown Center On Aging, University of Kentucky, Rm 575 Lee Todd Jr Bldg/U. Kentucky, 789 S. Limestone Ave, Lexington, KY, 40536, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA.
Nikhil B GhayalDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA.
Khine Zin AungSanders-Brown Center On Aging, University of Kentucky, Rm 575 Lee Todd Jr Bldg/U. Kentucky, 789 S. Limestone Ave, Lexington, KY, 40536, USA.
Xian WuSanders-Brown Center On Aging, University of Kentucky, Rm 575 Lee Todd Jr Bldg/U. Kentucky, 789 S. Limestone Ave, Lexington, KY, 40536, USA.
Panhavuth PheSanders-Brown Center On Aging, University of Kentucky, Rm 575 Lee Todd Jr Bldg/U. Kentucky, 789 S. Limestone Ave, Lexington, KY, 40536, USA.
Gregory A JichaSanders-Brown Center On Aging, University of Kentucky, Rm 575 Lee Todd Jr Bldg/U. Kentucky, 789 S. Limestone Ave, Lexington, KY, 40536, USA.
Allison M NeltnerSanders-Brown Center On Aging, University of Kentucky, Rm 575 Lee Todd Jr Bldg/U. Kentucky, 789 S. Limestone Ave, Lexington, KY, 40536, USA.
Jessalin R C ArcherSanders-Brown Center On Aging, University of Kentucky, Rm 575 Lee Todd Jr Bldg/U. Kentucky, 789 S. Limestone Ave, Lexington, KY, 40536, USA.
Maria M CorradaDepartment of Neurology, University of California, Irvine, CA, USA.
Claudia H KawasDepartment of Neurology, University of California, Irvine, CA, USA.
S Ahmad SajjadiDepartment of Neurology, University of California, Irvine, CA, USA.
Davis C WoodworthDepartment of Neurology, University of California, Irvine, CA, USA.
Syed A BukhariDepartment of Pathology, Stanford University, Stanford, CA, USA.
Thomas J MontineDepartment of Pathology, Stanford University, Stanford, CA, USA.
David W FardoSanders-Brown Center On Aging, University of Kentucky, Rm 575 Lee Todd Jr Bldg/U. Kentucky, 789 S. Limestone Ave, Lexington, KY, 40536, USA.
Peter T NelsonSanders-Brown Center On Aging, University of Kentucky, Rm 575 Lee Todd Jr Bldg/U. Kentucky, 789 S. Limestone Ave, Lexington, KY, 40536, USA. peter.nelson@uky.edu.

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2M
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GALASKO, DOUGLAS R · 1985 to 2018
$55.4M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
National Institutes on Health, United States R01 AG061111, R01 AG057187, P30 AG072946, RF1 NS118584, T32 AG078110, R01 AG021055, P30 AG066519NCI NIH HHS R01 CA129769NCRR NIH HHS UL1 RR029893NHGRI NIH HHS U01 HG004610NHGRI NIH HHS U01 HG006375NIA NIH HHS P01 AG002219NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG010491NIA NIH HHS P01 AG019724NIA NIH HHS P20 AG068082NIA NIH HHS P30 AG008017NIA NIH HHS P30 AG008051NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010129NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG012300NIA NIH HHS P30 AG013846NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG028377NIA NIH HHS P30 AG028383NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066508NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066512NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG066519NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072931NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072947NIA NIH HHS P30 AG072958NIA NIH HHS P30 AG072959NIA NIH HHS P30 AG072972NIA NIH HHS P30 AG072973NIA NIH HHS P30 AG072975NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072977NIA NIH HHS P30 AG072978NIA NIH HHS P30 AG072979NIA NIH HHS P30 AG086401NIA NIH HHS P30 AG086404NIA NIH HHS P50 AG005128NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005133NIA NIH HHS P50 AG005134NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG005138NIA NIH HHS P50 AG005142NIA NIH HHS P50 AG005144NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008671NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016570NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG016582NIA NIH HHS P50 AG023501NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG033514NIA NIH HHS R01 AG012101NIA NIH HHS R01 AG013616NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017173NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG019085NIA NIH HHS R01 AG019757NIA NIH HHS R01 AG020688NIA NIH HHS R01 AG021055NIA NIH HHS R01 AG021547NIA NIH HHS R01 AG022374NIA NIH HHS R01 AG025259NIA NIH HHS R01 AG026916NIA NIH HHS R01 AG027944NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG030653NIA NIH HHS R01 AG031581NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG035137NIA NIH HHS R01 AG041232NIA NIH HHS R01 AG041718NIA NIH HHS R01 AG041797NIA NIH HHS R01 AG057187NIA NIH HHS R01 AG061111NIA NIH HHS R01 AG062706NIA NIH HHS R01 AG079280NIA NIH HHS R01 AG082730NIA NIH HHS R37 AG015473NIA NIH HHS RC2 AG036502NIA NIH HHS RC2 AG036528NIA NIH HHS RF1 AG082339NIA NIH HHS T32 AG078110NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG010483NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG026395NIA NIH HHS U24 AG041689NIA NIH HHS U24 AG072122NIMH NIH HHS P50 MH060451NIMH NIH HHS R01 MH080295NINDS NIH HHS P50 NS039764NINDS NIH HHS R01 NS059873NINDS NIH HHS RF1 NS118584Wellcome Trust
6 · The paper itself

Abstract

A diagnostic rubric is required to distinguish between limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In LATE-NC Stage 3, TDP-43 proteinopathy is present in the middle frontal gyrus (MFG), thus posing a potential diagnostic challenge in differentiating these severe LATE-NC cases from FTLD-TDP. LATE-NC Stage 3 cases and other TDP-43 proteinopathies were analyzed from the University of Kentucky (total n = 514 with TDP-43 pathology assessed), The 90+ Study at the University of California Irvine (n = 458), and the Mayo Clinic (n = 5067) brain banks. Digital pathology was used to quantify pathology burden in a select subset of cases (n = 51), complemented by a previously-described manual counting method and expert neuropathologic examinations to evaluate qualitative features such as FTLD-TDP types and subtypes of neuronal cytoplasmic inclusions (NCIs). To evaluate clinical and genetic characteristics of LATE-NC Stage 3, data were analyzed from the National Alzheimer's Coordinating Center (NACC) Neuropathology Data set and correlated with findings from the Alzheimer's Disease Genetics Consortium (ADGC). When using TDP-43 proteinopathy quantification in the MFG as a diagnostic criterion, more than 90% of cases could be classified as either LATE-NC Stage 3 or FTLD-TDP. Diagnostically challenging scenarios included a subset of FTLD-TDP Type B cases with relatively mild MFG TDP-43 pathology and a novel non-LATE-NC, non-FTLD-TDP pathologic subtype with severe MFG TDP-43 pathology. Taking these potential pitfalls into account, a classification schema was developed that could correctly diagnose all included cases. There was no difference in the Alzheimer's disease pathological load in LATE-NC Stages 2 versus 3. In genetic analyses, the GRN (rs5848) risk allele was preferentially associated with LATE-NC Stage 3, whereas TMEM106B and APOE risk-associated variants were not. In conclusion, LATE-NC Stage 3 could be differentiated reliably from FTLD-TDP and other TDP-43-opathies, based on a data-driven diagnostic rubric.

Indexed as

BrainFrontotemporal Lobar DegenerationTDP-43 ProteinopathiesAgedAged, 80 and overDementiaDiagnosis, DifferentialDNA-Binding ProteinsFemaleHumansInclusion BodiesMaleMiddle AgedDNA-Binding ProteinsTARDBP protein, humanALSARTAGFTLD-MNDLNTrs1990622ScanScope

Identifiers

PMID40293530
PMCPMC12037668

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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.