Evidence mapPaperPMID 40900992Full record

ArticleFrontiers in aging neuroscience2025

Accelerated midlife endocrine and bioenergetic brain aging in APOE4 females.

Tian Wang, Zisu Mao, Yuan Shang, Simona Merlini, Francesca Vitali, Jean-Paul Wiegand, Roberta Diaz Brinton

Abstract read
In one paragraph

Article in Frontiers in aging neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Sex differences in brain glucose metabolism and Alzheimer's disease risk and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  3. Addition of humanized APP to humanizedbioRxiv : the preprint server for biology · 2026
    Article
  4. Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. 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

7 authors.

Tian WangCenter for Innovation in Brain Science, University of Arizona, Tucson, AZ, United States.
Zisu MaoCenter for Innovation in Brain Science, University of Arizona, Tucson, AZ, United States.
Yuan ShangCenter for Innovation in Brain Science, University of Arizona, Tucson, AZ, United States.
Simona MerliniCenter for Innovation in Brain Science, University of Arizona, Tucson, AZ, United States.
Francesca VitaliCenter for Innovation in Brain Science, University of Arizona, Tucson, AZ, United States.
Jean-Paul WiegandCenter for Innovation in Brain Science, University of Arizona, Tucson, AZ, United States.
Roberta Diaz BrintonCenter for Innovation in Brain Science, University of Arizona, Tucson, AZ, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Female sex, age, and APOE4 genotype are the greatest risk factors for Alzheimer's disease. Using a translational perimenopause mouse model based on human Stages of Reproductive Aging Works (STRAW) criteria, we investigated the impact of APOE genotype on female midlife endocrine aging, peripheral metabolic indicators, brain bioenergetic pathways, mitochondrial function, neuroimmune activation, and myelination. Compared to APOE3 females, APOE4 females exhibited accelerated endocrine aging that was coincident with failure to mount adaptive bioenergetic reprogramming and significant decline in mitochondrial function that were coupled with increased immune activation and demyelination in brain. In women, APOE4 was associated with early menopause. Further, APOE4 women experiencing early menopause exhibited the highest risk of Alzheimer's. These results provide plausible mechanistic pathways underlying the earlier emergence and greater risk of Alzheimer's in APOE4 postmenopausal females. Collectively, these findings support midlife as a critical window for intervention to prevent or delay the onset of the prodromal stage of Alzheimer's disease in APOE4 carriers.

Indexed as

Alzheimer′sAPOE4Menopausemitochondrial functionneuroinflammationwomen

Identifiers

PMID40900992
PMCPMC12399568

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.