Evidence map›Paper›PMID 27569580›Full record

ArticleNeurobiology of disease2016

Sex-related dimorphism in dentate gyrus atrophy and behavioral phenotypes in an inducible tTa:APPsi transgenic model of Alzheimer's disease.

Tatiana Melnikova, DaMin Park, Lauren Becker, Deidre Lee, Eugenia Cho, Nuzhat Sayyida, Jing Tian, Karen Bandeen-Roche, David R Borchelt, Alena V Savonenko

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

Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

15 citing papers in PubMed, 29 citations in OpenAlex.

  1. Twenty years of therapeutic development in tauopathy mouse models: a scoping review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Age-Dependent Remarkable Regenerative Potential of the Dentate Gyrus Provided by Intrinsic Stem Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
  11. Animal Models of Psychosis in Alzheimer Disease.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2020
    Review
  12. Review
  13. Article
  14. Article
  15. 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

10 authors at 3 institutions in 1 country.

Tatiana MelnikovaDepartment of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 558, Baltimore, MD 21205, USA. Electronic address: tmelnik1@jhmi.edu.
DaMin ParkDepartment of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 558, Baltimore, MD 21205, USA. Electronic address: dpark39@jhmi.edu.
Lauren BeckerDepartment of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 558, Baltimore, MD 21205, USA. Electronic address: lnb785@gmail.com.
Deidre LeeDepartment of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 558, Baltimore, MD 21205, USA. Electronic address: lee.deidre@gmail.com.
Eugenia ChoDepartment of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 558, Baltimore, MD 21205, USA. Electronic address: eugeniacho87@gmail.com.
Nuzhat SayyidaDepartment of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 558, Baltimore, MD 21205, USA. Electronic address: naz0789@gmail.com.
Jing TianDepartment of Biostatistics, School of Public Health, The Johns Hopkins University, 615 N Wolfe St E3527, Baltimore, MD 21205, USA. Electronic address: jtian4@jhmi.edu.
Karen Bandeen-RocheDepartment of Biostatistics, School of Public Health, The Johns Hopkins University, 615 N Wolfe St E3527, Baltimore, MD 21205, USA. Electronic address: kbandeen@jhsph.edu.
David R BorcheltDepartment of Neuroscience, Center for Translational Research in Neurodegenerative Disease, McKnight Brain Institute, University of Florida, 100 Newell Drive, Gainesville, FL 32610, USA. Electronic address: drb1@ufl.edu.
Alena V SavonenkoDepartment of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross 558, Baltimore, MD 21205, USA. Electronic address: asavone1@jhmi.edu.
Johns Hopkins University · USBloomberg (United States) · USUniversity of Florida · US

Funding

'T V ASSESSMENT - MEMORY DISORDERED PATIENTS'P50AG005146 · NIA · JOHNS HOPKINS UNIVERSITY · PI HUGANIR, RICHARD L · 1985 to 2019
$37.6M
Repair and Regeneration in Alzheimer's DiseaseR01NS047225 · NINDS · UNIVERSITY OF FLORIDA · PI BORCHELT, DAVID R, SAVONENKO, ALENA · 2004 to 2012
$3.2M
NIA NIH HHS P50 AG005146NINDS NIH HHS R01 NS047225
6 · The paper itself

Abstract

Sex differences are a well-known phenomenon in Alzheimer's disease (AD), with women having a higher risk for AD than men. Many AD mouse models display a similar sex-dependent pattern, with females showing earlier cognitive deficits and more severe neuropathology than males. However, whether those differences are relevant to human disease is unclear. Here we show that in AD mouse models that overexpress amyloid precursor protein (APP) under control of the prion protein promoter (PrP), female transgenic mice have higher APP expression than males, complicating interpretations of the role of sex-related factors in such models. By contrast, in a tTa:APPsi model, in which APP expression is driven by the tetracycline transactivator (tTa) from the CaMKIIα promoter, there are no sex-related differences in expression or processing of APP. In addition, the levels of Aβ dimers and tetramers, as well as Aβ peptide accumulation, are similar between sexes. Behavioral testing demonstrated that both male and female tTa:APPsi mice develop age-dependent deficits in spatial recognition memory and conditional freezing to context. These cognitive deficits were accompanied by habituation-associated hyperlocomotion and startle hyper-reactivity. Significant sex-related dimorphisms were observed, due to females showing earlier onsets of the deficits in conditioned freezing and hyperlocomotion. In addition, tTa:APPsi males but not females demonstrated a lack of novelty-induced activation. Both males and females showed atrophy of the dentate gyrus (DG) of the dorsal hippocampus, associated with widening of the pyramidal layer of the CA1 area in both sexes. Ventral DG was preserved. Sex-related differences were limited to the DG, with females showing more advanced degeneration than males. Collectively, our data show that the tTa:APPsi model is characterized by a lack of sex-related differences in APP expression, making this model useful in deciphering the mechanisms of sex differences in AD pathogenesis. Sex-related dimorphisms observed in this model under conditions of equal APP expression between sexes suggest a higher sensitivity of females to the effects of APP and/or Aβ production.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsAtrophyConditioning, PsychologicalDentate GyrusDisease Models, AnimalFearFemaleHumansLocomotionMaleMiceMice, TransgenicModels, BiologicalAmyloid beta-PeptidesAmyloid beta-Protein PrecursorPresenilin-1TetracyclineAPP expressionAβ oligomerscontextual feardorsal dentate gyrusgender differenceshabituation-associated hyperactivitynovelty-induced activationsex dimorphismtTa effects

Identifiers

PMID27569580
PMCPMC6457346
OpenAlexW2511102271

What OpenQuestion holds

Textmetadata
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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.