Evidence map›Paper›PMID 26582141›Full record

ArticleFrontiers in aging neuroscience2015

Differential contributions of ApoE4 and female sex to BACE1 activity and expression mediate Aβ deposition and learning and memory in mouse models of Alzheimer's disease.

Xu Hou, Samuel O Adeosun, Qinli Zhang, Brett Barlow, Melissa Brents, Baoying Zheng, Junming Wang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in aging neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

17 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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  6. Article
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  8. Frontiers in aging neuroscience · 2023
    Article
  9. Article
  10. Alzheimer's pathogenic mechanisms and underlying sex difference.Cellular and molecular life sciences : CMLS · 2021
    Review
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  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. The multifaceted roles of the transcription factorAlzheimer's & dementia (New York, N. Y.)
    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

7 authors at 2 institutions in 1 country.

Xu HouProgram in Neuroscience, University of Mississippi Medical Center, Jackson MS, USA.
Samuel O AdeosunDepartment of Pathology, University of Mississippi Medical Center, Jackson MS, USA.
Qinli ZhangDepartment of Pathology, University of Mississippi Medical Center, Jackson MS, USA.
Brett BarlowDepartment of Pathology, University of Mississippi Medical Center, Jackson MS, USA.
Melissa BrentsDepartment of Pathology, University of Mississippi Medical Center, Jackson MS, USA.
Baoying ZhengDepartment of Pathology, University of Mississippi Medical Center, Jackson MS, USA.
Junming WangProgram in Neuroscience, University of Mississippi Medical Center, Jackson MS, USA ; Department of Pathology, University of Mississippi Medical Center, Jackson MS, USA ; Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson MS, USA ; Center of Memory Impairment and Neurodegenerative Dementia, University of Mississippi Medical Center, Jackson MS, USA.
Jackson Memorial Hospital · USUniversity of Mississippi Medical Center · US

Funding

Center for Psychiatric NeuroscienceP30GM103328 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI STOCKMEIER, CRAIG ALLEN · 2013 to 2017
$5.5M
NIGMS NIH HHS P30 GM103328
6 · The paper itself

Abstract

Alzheimer's disease (AD), the most common form of dementia, disproportionately affects women in both prevalence and severity. This increased vulnerability to AD in women is strongly associated with age-related ovarian hormone loss and apolipoprotein E 4 allele (ApoE4), the most important genetic risk factor for sporadic AD. Up to date, the mechanism involved in the interaction between ApoE4 and sex/gender in AD is still unclear. This study evaluated the sex-dependent ApoE4 effects on learning and memory, Aβ deposition and potential mechanisms, using mice bearing both sporadic (ApoE4) and familial (APPSwe, PS1M146V, tauP301L; 3xTg) AD risk factors and compared with sex- and age-matched 3xTg or nonTg mice. Compared to nonTg mice, transgenic mice of both sexes showed spatial learning and memory deficits in the radial arm water maze and novel arm discrimination tests at 20 months of age. However, at 10 months, only ApoE4/3xTg mice showed significant learning and memory impairment. Moreover, molecular studies of hippocampal tissue revealed significantly higher protein levels of Aβ species, β-site APP cleavage enzyme (BACE1) and Sp1, a transcription factor of BACE1, in female ApoE4/3xTg when compared with female nonTg, female 3xTg, and male ApoE4/3xTg mice. Significantly increased BACE1 enzymatic activities were observed in both male and female mice carrying ApoE4; however, only the females showed significant higher BACE1 expressions. Together, these data suggest that ApoE4 allele is associated with increased BACE1 enzymatic activity, while female sex plays an important role in increasing BACE1 expression. The combination of both provides a molecular basis for high Aβ pathology and the resultant hippocampus-dependent learning and memory deficits in female ApoE4 carriers.

Indexed as

Alzheimer’s DiseaseApoE4BACE1learning and memorysex-dependent effect

Identifiers

PMID26582141
PMCPMC4628114
OpenAlexW2180877495

What OpenQuestion holds

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LicenceCC BY
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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.