Evidence map›Paper›PMID 39858593›Full record

ArticleGenes2025

Production of Amyloid-β in the Aβ-Protein-Precursor Proteolytic Pathway Is Discontinued or Severely Suppressed in Alzheimer's Disease-Affected Neurons: Contesting the 'Obvious'.

Vladimir Volloch, Sophia Rits-Volloch

Abstract read
In one paragraph

Article in Genes, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

2 authors.

Vladimir VollochDepartment of Developmental Biology, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Sophia Rits-VollochDivision of Molecular Medicine, Children's Hospital, Boston, MA 02115, USA.

Funding

STRUCTURE OF TYPE I AND TYPE II PROCOLLAGENSR01AR036819 · NIAMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI OLSEN, BJORN REINO · 1986 to 2016
$8.7M
GLOBIN MRNA HYPERPRODUCTION IN RESPONSE TO ANEMIAR21GM056179 · NIGMS · BOSTON BIOMEDICAL RESEARCH INSTITUTE · PI VOLLOCH, VLADIMIR Z · 1997 to 1997
–
NIAMS NIH HHS R01 AR036819NIGMS NIH HHS R21 GM056179NIH HHS NIH R21 GM056179NIH HHS NIH R21 GM056179; NIH RO1 AR036819
6 · The paper itself

Abstract

A notion of the continuous production of amyloid-β (Aβ) via the proteolysis of Aβ-protein-precursor (AβPP) in Alzheimer's disease (AD)-affected neurons constitutes both a cornerstone and an article of faith in the Alzheimer's research field. The present Perspective challenges this assumption. It analyses the relevant empirical data and reaches an unexpected conclusion, namely that in AD-afflicted neurons, the production of AβPP-derived Aβ is either discontinued or severely suppressed, a concept that, if proven, would fundamentally change our understanding of the disease. This suppression, effectively self-suppression, occurs in the context of the global inhibition of the cellular cap-dependent protein synthesis as a consequence of the neuronal integrated stress response (ISR) elicited by AβPP-derived intraneuronal Aβ (

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorNeuronsAnimalsHumansMiceProteolysisAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAD as the disease of the neuronal ISRAmyloid Cascade Hypothesis 2.0 (ACH2.0)AβPP-independent generation of the C99 fragmentC99 as the driver of ADconcurrent inhibition of the ISR and activation of BACE1 and BACE2 as composite AD therapyconventional and unconventional Alzheimer’s disease (AD)design of AD modelsISR-mediated suppression of the AβPP proteolytic pathway and dyshomeostasis of AβPP in AD-affected neuronsneuronal integrated stress response (ISR)RNA-dependent amplification of human AβPP mRNA

Identifiers

PMID39858593
PMCPMC11764795

What Socratic holds

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LicenceCC BY
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 Socratic graph.