ArticleBiology of sex differences2025
Consideration of sex as a biological variable over the history of the 5xFAD Alzheimer's Disease mouse model.
Article in Biology of sex differences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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.
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.
Who cites it
2 citing papers in PubMed.
- Glial cytokine modulation improves sleep and circadian disruption in female SAA knock-in mice of Alzheimer's-related pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Impaired behavioral flexibility and coping strategy shifts in 5xFAD mice in the novel Destruction-Building Test.Frontiers in behavioral neuroscience · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
backgroundWomen are nearly twice as likely to be diagnosed with Alzheimer's Disease (AD) over their lifetime. However, historically, preclinical studies utilizing AD rodent models to define new therapeutic targets in AD treatment have neglected to consider the confounding influence of subject sex leading to a lack of mechanistic insight into the biological underpinnings of sex bias in AD.
methodsHere, we tracked choice of subject sex over the twenty-year history of the 5xFAD mouse, one of the most frequently cited pre-clinical AD models. We analyzed 1,330 primary research articles indexed on PubMed and recorded information provided regarding subject sex and/or as a rationale for not including datasets separated by sex, if noted. Trends were then plotted as a function of time ending in December 2024.
resultsIn the last 15 years, the number of published manuscripts on the 5xFAD model omitting information on subject sex has progressively declined. However, the proportion of studies utilizing either males only (29%) or combining data from both sexes (24%) far surpasses studies acknowledging sex as a biological variable (SABV) (< 12%) with no significant changes noted over time. On average, the ratio of male only: female only studies of 5xFAD mice hovered around 2:1. The most frequently cited reason for omitting sex-based analyses was either a lack of sex differences found (29%), accelerated development of plaque burden in 5xFAD females (17%), or the possibility of within- or between-sex variability (15%). Mention of SABV has steadily increased in studies utilizing 5xFAD mice peaking at ~ 30% of manuscripts published in 2024. However, two key confounds in the 5xFAD model, including the potential impact of an estrogen response element (ERE) and parental imprinting in the Thy1 promoter driving transgene expression, have been largely ignored.
conclusionsThe 5xFAD model represents a compelling example of how neglecting to recognize the impact of biological sex on neural function can compromise study design and data interpretation. Given sex-dependent Thy1 promoter regulation may skew phenotypic outcomes, investigators should judiciously interpret sex differences observed in any AD mouse utilizing the Thy1 promoter to drive transgene expression.
Indexed as
Identifiers
What Socratic holds
Registered trials
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.