ArticleTranslational psychiatry2023
Sex difference in evolution of cognitive decline: studies on mouse model and the Dominantly Inherited Alzheimer Network cohort.
Article in Translational psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Article
- Early Onset Memory Deficit of WMI Rats Compared to Their Nearly Isogenic WLIs Is Reversed by Enriched Environment in Females.Genes, brain, and behavior · 2025Article
- Article
- Sex-related differences in genetically determined Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- In Vivo Tau and Neurodegeneration Imaging in a Family With the Presenilin 1 Met146Leu Pathogenic Variant.Neurology · 2024Article
- Early hippocampal hyperexcitability and synaptic reorganization in mouse models of amyloidosis.iScience · 2024Article
- Article
- Reconsidering repurposing: long-term metformin treatment impairs cognition in Alzheimer's model mice.Translational psychiatry · 2024Article
- Sex differences in the relationship between depression and Alzheimer's disease-mechanisms, genetics, and therapeutic opportunities.Frontiers in aging neuroscience · 2024Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 5 countries.
Funding
Abstract
Women carry a higher burden of Alzheimer's disease (AD) compared to men, which is not accounted entirely by differences in lifespan. To identify the mechanisms underlying this effect, we investigated sex-specific differences in the progression of familial AD in humans and in APPswe/PS1ΔE9 mice. Activity dependent protein translation and associative learning and memory deficits were examined in APPswe/PS1ΔE9 mice and wild-type mice. As a human comparator group, progression of cognitive dysfunction was assessed in mutation carriers and non-carriers from DIAN (Dominantly Inherited Alzheimer Network) cohort. Female APPswe/PS1ΔE9 mice did not show recall deficits after contextual fear conditioning until 8 months of age. Further, activity dependent protein translation and Akt1-mTOR signaling at the synapse were impaired in male but not in female mice until 8 months of age. Ovariectomized APPswe/PS1ΔE9 mice displayed recall deficits at 4 months of age and these were sustained until 8 months of age. Moreover, activity dependent protein translation was also impaired in 4 months old ovariectomized APPswe/PS1ΔE9 mice compared with sham female APPswe/PS1ΔE9 mice. Progression of memory impairment differed between men and women in the DIAN cohort as analyzed using linear mixed effects model, wherein men showed steeper cognitive decline irrespective of the age of entry in the study, while women showed significantly greater performance and slower decline in immediate recall (LOGIMEM) and delayed recall (MEMUNITS) than men. However, when the performance of men and women in several cognitive tasks (such as Wechsler's logical memory) are compared with the estimated year from expected symptom onset (EYO) we found no significant differences between men and women. We conclude that in familial AD patients and mouse models, females are protected, and the onset of disease is delayed as long as estrogen levels are intact.
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