Evidence map›Paper›PMID 38263854›Full record

ArticleAnnals of clinical and translational neurology2024

Tau maturation in the clinicopathological spectrum of Lewy body and Alzheimer's disease.

Sanaz Arezoumandan, Katheryn A Q Cousins, Daniel T Ohm, MaKayla Lowe, Min Chen, James Gee, Jeffrey S Phillips, Corey T McMillan, Kelvin C Luk, Andres Deik and 9 more

Open access · goldAbstract read
In one paragraph

Article in Annals of clinical and translational neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
2.9field-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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
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  3. Article
  4. Where do PDD and DLB SYNdromes fit in neuronal alpha-SYNuclein biological frameworks?Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
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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

19 authors at 1 institution in 1 country.

Sanaz ArezoumandanDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0001-6569-9009
Katheryn A Q CousinsDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0003-1879-2766
Daniel T OhmDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
MaKayla LoweDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Min ChenDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
James GeeDepartment of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jeffrey S PhillipsDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0003-0079-9441
Corey T McMillanDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Kelvin C LukDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Andres DeikDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Meredith A SpindlerDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Thomas F TropeaDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Daniel WeintraubDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0003-0633-7168
David A WolkDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Murray GrossmanDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Virginia LeeDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Alice S Chen-PlotkinDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Edward B LeeDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
David J IrwinDepartment of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-5599-5098
University of Pennsylvania · US

Funding

Research Education ComponentP30AG072979 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Corey T McMillan · 2021 to 2026
$24.8M
Understanding Environmental Contributions to Heterogeneity in bvFTD.P01AG066597 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Edward Byung-Ha Lee · 2020 to 2026
$18.8M
Project IV "Tackling Heterogeneity of Cognitive Trajectory in LBD"U19AG062418 · NIA · UNIVERSITY OF PENNSYLVANIA · PI XIE, SHARON XIANGWEN · 2019 to 2023
$18.1M
Project IV: In Vivo Dissection of Genetic Modifiers on Different Stages of SynucleinopathyP01AG084497 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DANIEL WEINTRAUB · 2024 to 2026
$15.2M
Pathogenesis of TauopathiesR01AG076434 · NIA · UNIVERSITY OF PENNSYLVANIA · PI VIRGINIA M LEE · 2023 to 2026
$3.0M
The Role of Alzheimer's Disease Genetic Risk in Predicting Parkinson's Disease DementiaK23NS114167 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI TROPEA, THOMAS FRANCIS · 2020 to 2024
$985k
NIA NIH HHS P01 AG066597NIA NIH HHS P01 AG084497NIA NIH HHS P30 AG072979NIA NIH HHS R01 AG076434NIA NIH HHS U19 AG062418NINDS NIH HHS K23 NS114167
6 · The paper itself

Abstract

objectiveAlzheimer's disease neuropathologic change and alpha-synucleinopathy commonly co-exist and contribute to the clinical heterogeneity of dementia. Here, we examined tau epitopes marking various stages of tangle maturation to test the hypotheses that tau maturation is more strongly associated with beta-amyloid compared to alpha-synuclein, and within the context of mixed pathology, mature tau is linked to Alzheimer's disease clinical phenotype and negatively associated with Lewy body dementia.

methodsWe used digital histology to measure percent area-occupied by pathology in cortical regions among individuals with pure Alzheimer's disease neuropathologic change, pure alpha-synucleinopathy, and a co-pathology group with both Alzheimer's and alpha-synuclein pathologic diagnoses. Multiple tau monoclonal antibodies were used to detect early (AT8, MC1) and mature (TauC3) epitopes of tangle progression. We used linear/logistic regression to compare groups and test the association between pathologies and clinical features.

resultsThere were lower levels of tau pathology (β = 1.86-2.96, p < 0.001) across all tau antibodies in the co-pathology group compared to the pure Alzheimer's pathology group. Among individuals with alpha-synucleinopathy, higher alpha-synuclein was associated with greater early tau (AT8 β = 1.37, p < 0.001; MC1 β = 1.2, p < 0.001) but not mature tau (TauC3 p = 0.18), whereas mature tau was associated with beta-amyloid (β = 0.21, p = 0.01). Finally, lower tau, particularly TauC3 pathology, was associated with lower frequency of both core clinical features and categorical clinical diagnosis of dementia with Lewy bodies.

interpretationMature tau may be more closely related to beta-amyloidosis than alpha-synucleinopathy, and pathophysiological processes of tangle maturation may influence the clinical features of dementia in mixed Lewy-Alzheimer's pathology.

Indexed as

Alzheimer DiseaseParkinson DiseaseSynucleinopathiesalpha-SynucleinAmyloid beta-PeptidesEpitopesHumansLewy Bodiestau Proteinsalpha-SynucleinAmyloid beta-PeptidesEpitopestau Proteins

Identifiers

PMID38263854
PMCPMC10963284
OpenAlexW4391170922

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.