Evidence map›Paper›PMID 26314631›Full record

ReviewNeuroscience2015

The keystone of Alzheimer pathogenesis might be sought in Aβ physiology.

D Puzzo, W Gulisano, O Arancio, A Palmeri

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
–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

50 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Microglial activation states and their implications for Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025
    Review
  6. Review
  7. Review
  8. Article
  9. Amyloid-β Effects on Peripheral Nerve: A New Model System.International journal of molecular sciences · 2023
    Article
  10. Structural polymorphism and cytotoxicity of brain-derived β-amyloid extracts.Protein science : a publication of the Protein Society · 2023
    Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Membrane Interactions and Toxicity by Misfolded Protein Oligomers.Frontiers in cell and developmental biology · 2021
    Review
  20. Article
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

4 authors.

D PuzzoDepartment of Biomedical and Biotechnological Sciences, Section of Physiology, Viale A. Doria 6 (ed. 2), University of Catania, Catania 95125, Italy. Electronic address: danypuzzo@yahoo.it.
W GulisanoDepartment of Biomedical and Biotechnological Sciences, Section of Physiology, Viale A. Doria 6 (ed. 2), University of Catania, Catania 95125, Italy.
O ArancioDepartment of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, 630 West 168th Street, Columbia University, New York, NY 10032, USA.
A PalmeriDepartment of Biomedical and Biotechnological Sciences, Section of Physiology, Viale A. Doria 6 (ed. 2), University of Catania, Catania 95125, Italy.

Funding

SUMOylation and Amyloid-beta elevationR01NS049442 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ARANCIO, OTTAVIO · 2005 to 2015
$4.1M
Endogenous amyloid-beta in synaptic function and memoryR01AG034248 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ARANCIO, OTTAVIO · 2010 to 2014
$1.7M
NIA NIH HHS AG034248NIA NIH HHS R01 AG034248NINDS NIH HHS NS049442NINDS NIH HHS R01 NS049442
6 · The paper itself

Abstract

For several years Amyloid-beta peptide (Aβ) has been considered the main pathogenetic factor of Alzheimer's disease (AD). According to the so called Amyloid Cascade Hypothesis the increase of Aβ triggers a series of events leading to synaptic dysfunction and memory loss as well as to the structural brain damage in the later stage of the disease. However, several evidences suggest that this hypothesis is not sufficient to explain AD pathogenesis, especially considering that most of the clinical trials aimed to decrease Aβ levels have been unsuccessful. Moreover, Aβ is physiologically produced in the healthy brain during neuronal activity and it is needed for synaptic plasticity and memory. Here we propose a model interpreting AD pathogenesis as an alteration of the negative feedback loop between Aβ and its physiological receptors, focusing on alpha7 nicotinic acetylcholine receptors (α7-nAchRs). According to this vision, when Aβ cannot exert its physiological function a negative feedback mechanism would induce a compensatory increase of its production leading to an abnormal accumulation that reduces α7-nAchR function, leading to synaptic dysfunction and memory loss. In this perspective, the indiscriminate Aβ removal might worsen neuronal homeostasis, causing a further impoverishment of learning and memory. Even if further studies are needed to better understand and validate these mechanisms, we believe that to deepen the role of Aβ in physiological conditions might represent the keystone to elucidate important aspects of AD pathogenesis.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsHumansSignal TransductionAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAlzheimer’s diseaseAmyloid-beta peptidememorynAchRssynaptic plasticity

Identifiers

PMID26314631
PMCPMC4591241

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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.