Evidence map›Paper›PMID 23312564›Full record

ArticleBiological psychiatry2013

Mifepristone alters amyloid precursor protein processing to preclude amyloid beta and also reduces tau pathology.

David Baglietto-Vargas, Rodrigo Medeiros, Hilda Martinez-Coria, Frank M LaFerla, Kim N Green

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biological psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 5% 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

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.

  1. Pooled it
  2. Review
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  8. Experimental laboratory models as tools for understanding modifiable dementia risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Review
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  15. Article
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  17. Gut feelings: the microbiota-gut-brain axis on steroids.American journal of physiology. Gastrointestinal and liver physiology · 2022
    Review
  18. Review
  19. Enduring glucocorticoid-evoked exacerbation of synaptic plasticity disruption in male rats modelling early Alzheimer's disease amyloidosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021
    Article
  20. SPG302 Reverses Synaptic and Cognitive Deficits Without Altering Amyloid or Tau Pathology in a Transgenic Model of Alzheimer's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

David Baglietto-VargasDepartment of Neurobiology and Behavior, University of California, Irvine, USA.
Rodrigo Medeiros
Hilda Martinez-Coria
Frank M LaFerla
Kim N Green
University of California, Irvine · US

Funding

UC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2000 to 2019
$37.0M
Gene Interactions in a Model of Alzheimer's DiseaseR01AG021982 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2003 to 2012
$3.3M
NIA NIH HHS AG-021982NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG16573NIA NIH HHS R01 AG021982
6 · The paper itself

Abstract

backgroundIncreased circulating glucocorticoids are features of both aging and Alzheimer's disease (AD), and increased glucocorticoids accelerate the accumulation of AD pathologies. Here, we analyzed the effects of the glucocorticoid receptor antagonist mifepristone (RU486) in the 3xTg-AD mouse model at an age where hippocampal damage leads to high circulating corticosterone levels.

methodsThe effects of mifepristone were investigated in 3xTg-AD mice using a combination of biochemical, histological, and behavior analyses.

resultsMifepristone treatment rescues the pathologically induced cognitive impairments and markedly reduces amyloid beta (Aβ)-load and levels, as well as tau pathologies. Analysis of amyloid precursor protein (APP) processing revealed concomitant decreases in both APP C-terminal fragments C99 and C83 and the appearance of a larger 17-kDa C-terminal fragment. Hence, mifepristone induces a novel C-terminal cleavage of APP that prevents it being cleaved by α- or β-secretase, thereby precluding Aβ generation in the central nervous system; this cleavage and the production of the 17-kDa APP fragment was generated by a calcium-dependent cysteine protease. In addition, mifepristone treatment also reduced the phosphorylation and accumulation of tau, concomitant with reductions in p25. Notably, deficits in cyclic-AMP response element-binding protein signaling were restored with the treatment.

conclusionsThese preclinical results point to a potential therapeutic role for mifepristone as an effective treatment for AD and further highlight the impact the glucocorticoid system has as a regulator of Aβ generation.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBrainCREB-Binding ProteinHormone AntagonistsMaleMaze LearningMiceMice, TransgenicMifepristonetau ProteinsAmyloid beta-PeptidesAmyloid beta-Protein PrecursorCREB-Binding ProteinHormone AntagonistsMifepristonetau Proteins3xTg-ADAlzheimer's diseaseAmyloid betaglucocorticoidsmifepristonetau

Identifiers

PMID23312564
PMCPMC3633722
OpenAlexW1991347149

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.