Evidence map›Paper›PMID 41388803›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

PP2A methylesterase, PME-1, and PP2A methyltransferase, LCMT-1, control sensitivity to impairments caused by injury-related oligomeric tau.

Sowmya N Sundaresh, Edward W Vogel, Christopher D Hue, Hong Zhang, Anna Staniszewski, Hanna L Berman, Zafar Gill, Kesava Asam, Siqi Liang, Liwei Shen and 8 more

Erratum issuedAbstract read
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In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Sowmya N SundareshDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.
Edward W VogelDepartment of Biomedical Engineering, Columbia University, New York, New York, USA.
Christopher D HueDepartment of Biomedical Engineering, Columbia University, New York, New York, USA.
Hong ZhangDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.
Anna StaniszewskiDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.
Hanna L BermanDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.
Zafar GillDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.
Kesava AsamDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.
Siqi LiangDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.
Liwei ShenDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.
Madhumathi GnanaprakashDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.
Erica AcquaroneDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.
Antonio MasoneDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.
Mauro FàDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.
Nicholas M KanaanDepartment of Translational Neuroscience, Michigan State University, Grand Rapids, Michigan, USA.
Barclay MorrisonDepartment of Biomedical Engineering, Columbia University, New York, New York, USA.
Ottavio ArancioDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.
Russell E NichollsDepartment of Pathology and Cell Pathology, Columbia University, New York, New York, USA.

Funding

Paul G. Allen Frontiers Group 12347U.S. Department of Defense HT9425-23-1-0384U.S. Department of Defense W81XWH-12-1-0579U.S. Department of Defense W81XWH-15-1-0550
6 · The paper itself

Abstract

introductionOligomeric species of tau are a hallmark of Alzheimer's disease (AD). Given the evidence implicating protein phosphatase 2A (PP2A) in the molecular pathogenesis of tauopathies, we sought to determine whether manipulating the expression of enzymes that regulate PP2A activity, such as leucine carboxyl methyltransferase 1 (LCMT-1) and protein methylesterase 1 (PME-1), would alter pathological responses to oligomeric tau.

methodsWe tested the effect of LCMT-1 and PME-1 overexpression on cognitive and electrophysiological impairments caused by exposure to either recombinant oligomeric human tau or oligomeric tau prepared from mice subjected to blast-induced traumatic brain injury.

resultsWe found that LCMT-1 overexpression reduced sensitivity while PME-1 overexpression increased sensitivity to tau-induced impairments. Moreover, shockwave exposure increased the propensity of endogenous tau to form toxic oligomers. DISCUSSION: These results suggest that manipulating LCMT-1 or PME-1 activity may represent novel therapeutic approaches for disorders involving exposure to pathogenic forms of oligomeric tau. HIGHLIGHTS: LCMT-1 and PME-1 overexpression alters sensitivity to oligomeric tau-induced impairments. Blast-induced traumatic brain injury increases the propensity of tau to oligomerize. Pathogenic tau-induced cognitive impairments were dependent on its oligomeric form.

Indexed as

Brain Injuries, TraumaticCarboxylic Ester HydrolasesProtein O-MethyltransferaseProtein Phosphatase 2Tauopathiestau ProteinsAnimalsDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLCarboxylic Ester HydrolasesLCMT1 protein, humanProtein O-MethyltransferaseProtein Phosphatase 2protein phosphatase methylesterase-1tau ProteinsAlzheimer's diseasecognitive dysfunctionneurodegenerationprotein phosphatase 2Atautraumatic brain injury

Identifiers

PMID41388803
PMCPMC12701366

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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.