Evidence map›Paper›PMID 32610140›Full record

ArticleCell reports2020

Caspase Activation and Caspase-Mediated Cleavage of APP Is Associated with Amyloid β-Protein-Induced Synapse Loss in Alzheimer's Disease.

Goonho Park, Hoang S Nhan, Sheue-Houy Tyan, Yusuke Kawakatsu, Carolyn Zhang, Mario Navarro, Edward H Koo

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 3% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.

  1. Pooled it
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  15. Alzheimer's Disease andLife (Basel, Switzerland) · 2025
    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

7 authors at 2 institutions in 2 countries.

Goonho ParkDepartment of Neurosciences, University of California, San Diego, La Jolla, CA 92037, USA.
Hoang S NhanDepartment of Neurosciences, University of California, San Diego, La Jolla, CA 92037, USA.
Sheue-Houy TyanDepartment of Neurosciences, University of California, San Diego, La Jolla, CA 92037, USA.
Yusuke KawakatsuDepartment of Neurosciences, University of California, San Diego, La Jolla, CA 92037, USA.
Carolyn ZhangDepartment of Neurosciences, University of California, San Diego, La Jolla, CA 92037, USA.
Mario NavarroTumor Microenvironment and Cancer Immunology Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Edward H KooDepartment of Neurosciences, University of California, San Diego, La Jolla, CA 92037, USA; Departments of Medicine and Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117549, Singapore. Electronic address: edkoo@ucsd.edu.
University of California, San Diego · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Mechanisms of abeta induced dysfunction in hippocampal neuronal circuitryR01NS084324 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOO, EDWARD H., LEUTGEB, STEFAN · 2014 to 2018
$2.7M
Synaptic damage in models of beta-amyloid associated pathologyR01AG032179 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOO, EDWARD H. · 2007 to 2011
$1.6M
NIA NIH HHS P50 AG005131NIA NIH HHS R01 AG032179NINDS NIH HHS P30 NS047101NINDS NIH HHS R01 NS084324
6 · The paper itself

Abstract

Amyloid β-protein (Aβ) toxicity is hypothesized to play a seminal role in Alzheimer's disease (AD) pathogenesis. However, it remains unclear how Aβ causes synaptic dysfunction and synapse loss. We hypothesize that one mechanism of Aβ-induced synaptic injury is related to the cleavage of amyloid β precursor protein (APP) at position D664 by caspases that release the putatively cytotoxic C31 peptide. In organotypic slice cultures derived from mice with a knock-in mutation in the APP gene (APP D664A) to inhibit caspase cleavage, Aβ-induced synaptic injury is markedly reduced in two models of Aβ toxicity. Loss of dendritic spines is also attenuated in mice treated with caspase inhibitors. Importantly, the time-dependent dendritic spine loss is correlated with localized activation of caspase-3 but is absent in APP D664A cultures. We propose that the APP cytosolic domain plays an essential role in Aβ-induced synaptic damage in the injury pathway mediated by localized caspase activation.

Indexed as

Alzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsCaspase 3Caspase InhibitorsDendritic SpinesEnzyme ActivationGene Knock-In TechniquesHEK293 CellsHumansMice, Inbred C57BLMutationNeuroprotectionSynapsesAmyloid beta-Protein PrecursorCaspase 3Caspase InhibitorsAlzheimer’s diseaseAPPAPP C31caspasesynaptic injury

Identifiers

PMID32610140
PMCPMC7375398
OpenAlexW3040500087

What OpenQuestion holds

Textmetadata
LicenceTDM
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.