Evidence map›Paper›PMID 27723722›Full record

ArticleNature medicine2016

Caspase-2 cleavage of tau reversibly impairs memory.

Xiaohui Zhao, Linda A Kotilinek, Benjamin Smith, Chris Hlynialuk, Kathleen Zahs, Martin Ramsden, James Cleary, Karen H Ashe

Abstract read
PubMed Publisher
In one paragraph

Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed
12.7field-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

118 citing papers in PubMed, 181 citations in OpenAlex.

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  8. Asparagine endopeptidase (AEP) inhibitor formulation via zein-based nanoparticle improves the therapeutic efficacy toward Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
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  15. Exploring caspase functions in mouse models.Apoptosis : an international journal on programmed cell death · 2024
    Review
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58 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Xiaohui ZhaoN. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, Minnesota, USA.
Linda A KotilinekN. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, Minnesota, USA.
Benjamin SmithN. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, Minnesota, USA.
Chris HlynialukN. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, Minnesota, USA.
Kathleen ZahsN. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, Minnesota, USA.
Martin RamsdenN. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, Minnesota, USA.
James ClearyN. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, Minnesota, USA.
Karen H AsheN. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, Minnesota, USA.
University of Minnesota · USGeriatric Research Education and Clinical Center · US

Funding

EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Role of Tau Cleavage in TauopathyR01NS079374 · NINDS · UNIVERSITY OF MINNESOTA · PI ASHE, KAREN H · 2013 to 2016
$1.5M
In Search of the Molecular Basis of Memory Loss in TauopathyR01NS063214 · NINDS · UNIVERSITY OF MINNESOTA · PI ASHE, KAREN H · 2008 to 2011
$1.2M
NIA NIH HHS R01 AG017917NINDS NIH HHS R01 NS063214NINDS NIH HHS R01 NS079374
6 · The paper itself

Abstract

In Alzheimer's disease (AD) and other tauopathies, the tau protein forms fibrils, which are believed to be neurotoxic. However, fibrillar tau has been dissociated from neuron death and network dysfunction, suggesting the involvement of nonfibrillar species. Here we describe a novel pathological process in which caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines. The truncation product, Δtau314, resists fibrillation and is present at higher levels in brains from cognitively impaired mice and humans with AD. The expression of tau mutants that resisted caspase-2 cleavage prevented tau from infiltrating spines, dislocating glutamate receptors and impairing synaptic function in cultured neurons, and it prevented memory deficits and neurodegeneration in mice. Decreasing the levels of caspase-2 restored long-term memory in mice that had existing deficits. Our results suggest an overall treatment strategy for re-establishing synaptic function and restoring memory in patients with AD by preventing tau from accumulating in dendritic spines.

Indexed as

MemoryAlzheimer DiseaseAnimalsBlotting, WesternCaspase 2CaspasesCells, CulturedDendritic SpinesDisease Models, AnimalExcitatory Postsynaptic PotentialsHippocampusHumansMemory DisordersMiceMice, TransgenicMorpholinosCasp2 protein, mouseCaspase 2CaspasesMAPT protein, humanMorpholinosReceptors, Glutamatetau Proteins

Identifiers

PMID27723722
OpenAlexW2530330371

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.