Evidence map›Paper›PMID 28965829›Full record

ReviewNeuropharmacology2018

Reduced brain insulin signaling: A seminal process in Alzheimer's disease pathogenesis.

George S Bloom, John S Lazo, Andrés Norambuena

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Neuropharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. 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

3 authors.

George S BloomDepartment of Biology, University of Virginia, Charlottesville, VA, USA; Department of Cell Biology, University of Virginia, Charlottesville, VA, USA; Department of Neuroscience, University of Virginia, Charlottesville, VA, USA. Electronic address: gsb4g@virginia.edu.
John S LazoDepartment of Pharmacology, University of Virginia, Charlottesville, VA, USA; Department of Chemistry, University of Virginia, Charlottesville, VA, USA.
Andrés NorambuenaDepartment of Biology, University of Virginia, Charlottesville, VA, USA.

Funding

Linking Tau Structure to Its Functions and Mechanisms in Alzheimer’s DiseaseRF1AG051085 · NIA · UNIVERSITY OF VIRGINIA · PI BLOOM, GEORGE S · 2016 to 2016
$1.8M
NIA NIH HHS RF1 AG051085
6 · The paper itself

Abstract

The synaptic dysfunction and death of neurons that mediate memory and cognition account together for the behavioral symptoms of Alzheimer's disease (AD). Reduced insulin signaling in the brain is a hallmark of AD patients, even in the absence of systemic type 1 or type 2 diabetes, prompting some researchers to refer to AD as brain-specific, or type 3 diabetes. A key question that arises about this signature feature of AD is "how, if at all, does the brain's impaired ability to utilize insulin contribute to the behavioral deficits associated with AD?" The fact that type 2 diabetes is a risk factor for AD suggests a causative role for impaired insulin responsiveness in AD pathogenesis, but how that might occur at a detailed molecular level had been elusive. Here we review recent findings that mechanistically link soluble forms of amyloid-β (Aβ) and tau, the respective building blocks of the amyloid plaques and neurofibrillary tangles that accumulate in the brains of AD patients, with neuronal decline that is associated with poor insulin responsiveness and may begin long before AD symptoms become evident. We discuss how Aβ and tau work coordinately to deprive neurons of functionally accessible insulin receptors and dysregulate normal signaling by the protein kinase, mTOR. Finally, we suggest how newly gained knowledge about pathogenic signaling caused by reduced brain insulin signaling might be exploited for improved early detection and therapeutic intervention for AD. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'

Indexed as

Alzheimer DiseaseAnimalsBrainHumansInsulinInsulinAlzheimer's diseaseAmyloid-βInsulinmTORTau

Identifiers

PMID28965829
PMCPMC5876069

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.