Evidence map›Paper›PMID 40266681›Full record

ArticleeLife2025

APP β-CTF triggers cell-autonomous synaptic toxicity independent of Aβ.

Mengxun Luo, Jia Zhou, Cailu Sun, Wanjia Chen, Chaoying Fu, Chenfang Si, Yaoyang Zhang, Yang Geng, Yelin Chen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026
    Review
  4. Brain-Targeting siRNA Delivery to Tackle Alzheimer's Disease.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
    Review
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

9 authors.

Mengxun LuoInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Jia ZhouInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Cailu SunInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Wanjia ChenInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Chaoying FuInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Chenfang SiInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Yaoyang ZhangInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.ORCID https://orcid.org/0000-0001-5363-9834
Yang GengInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Yelin ChenInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.ORCID https://orcid.org/0000-0002-9793-2941

Funding

National Natural Science Foundation of China 31671044National Natural Science Foundation of China 91849204National Program on Key Research Project of China 2016YFA0501901Shanghai Municipal Science and Technology Major Project 2019SHZDZX02
6 · The paper itself

Abstract

Aβ is believed to play a significant role in synaptic degeneration observed in Alzheimer's disease and is primarily investigated as a secreted peptide. However, the contribution of intracellular Aβ or other cleavage products of its precursor protein (APP) to synaptic loss remains uncertain. In this study, we conducted a systematic examination of their cell-autonomous impact using a sparse expression system in rat hippocampal slice culture. Here, these proteins/peptides were overexpressed in a single neuron, surrounded by thousands of untransfected neurons. Surprisingly, we found that APP induced dendritic spine loss only when co-expressed with BACE1. This effect was mediated by β-CTF, a β-cleavage product of APP, through an endosome-related pathway independent of Aβ. Neuronal expression of β-CTF in mouse brains resulted in defective synaptic transmission and cognitive impairments, even in the absence of amyloid plaques. These findings unveil a β-CTF-initiated mechanism driving synaptic toxicity irrespective of amyloid plaque formation and suggest a potential intervention by inhibiting the endosomal GTPase Rab5.

Indexed as

Amyloid beta-PeptidesAmyloid beta-Protein PrecursorNeuronsSynapsesAlzheimer DiseaseAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesDendritic SpinesHippocampusMiceMice, Inbred C57BLrab5 GTP-Binding ProteinsRatsSynaptic TransmissionAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAspartic Acid Endopeptidasesrab5 GTP-Binding ProteinsAlzheimer's diseaseamyloid precursor proteinendosomemouseneuroscienceratsynapseβ-CTF

Identifiers

PMID40266681
PMCPMC12017768

What OpenQuestion holds

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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.