ArticlePloS one2020
Evidence in support of chromosomal sex influencing plasma based metabolome vs APOE genotype influencing brain metabolome profile in humanized APOE male and female mice.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Systematic review ofFrontiers in aging neuroscience · 2023Pooled it
- Sex differences in brain glucose metabolism and Alzheimer's disease risk and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- A ketogenic diet improves memory in females in the APOE4 mouse model of Alzheimer's disease.GeroScience · 2026Article
- APOE4 Accelerates Menopause-Associated Brain Metabolic Shift and Disrupts Bioenergetic Adaptation.bioRxiv : the preprint server for biology · 2026Article
- Association between apolipoprotein E gene polymorphisms and the effects of high-intensity interval training on body composition in university students.Frontiers in nutrition · 2026Article
- APOE4 accelerates menopause-associated brain metabolic shift and disrupts bioenergetic adaptation.Frontiers in aging neuroscience · 2026Article
- Humanized APOE mouse brain volume increases over age irrespective of sex and APOE genotype: implications for translational validity to the human.Frontiers in neuroscience · 2026Article
- Humanized APOE mouse brain volume increases over age irrespective of sex and APOE genotype: Implications for translational validity to the human.bioRxiv : the preprint server for biology · 2025Article
- Accelerated midlife endocrine and bioenergetic brain aging in APOE4 females.Frontiers in aging neuroscience · 2025Article
- Sex-related differences in genetically determined Alzheimer's disease.Frontiers in aging neuroscience · 2025Review
- Article
- Plasma lipidomics in early APP/PS1 female mouse model and its relationship with brain: Is it affected by the estrous cycle?Alzheimer's research & therapy · 2024Article
- Sex and Gender Differences in Alzheimer's Disease: Genetic, Hormonal, and Inflammation Impacts.International journal of molecular sciences · 2024Review
- Minding the Gap: Exploring Neuroinflammatory and Microglial Sex Differences in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Sex Modifies the Impact of Type 2 Diabetes Mellitus on the Murine Whole Brain Metabolome.Metabolites · 2023Article
- Predictive metabolic networks reveal sex- and APOE genotype-specific metabolic signatures and drivers for precision medicine in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- A long-term ketogenic diet in young and aged rats has dissociable effects on prelimbic cortex and CA3 ensemble activity.Frontiers in aging neuroscience · 2023Article
- Article
- Contributions of sex and genotype to exploratory behavior differences in an aged humanizedLearning & memory (Cold Spring Harbor, N.Y.) · 2022Article
- Sex and APOE Genotype Alter the Basal and Induced Inflammatory States of Primary Microglia from APOE Targeted Replacement Mice.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Late onset Alzheimer's disease (LOAD) is a progressive neurodegenerative disease with four well-established risk factors: age, APOE4 genotype, female chromosomal sex, and maternal history of AD. Each risk factor impacts multiple systems, making LOAD a complex systems biology challenge. To investigate interactions between LOAD risk factors, we performed multiple scale analyses, including metabolomics, transcriptomics, brain magnetic resonance imaging (MRI), and beta-amyloid assessment, in 16 months old male and female mice with humanized human APOE3 (hAPOE3) or APOE4 (hAPOE4) genes. Metabolomic analyses indicated a sex difference in plasma profile whereas APOE genotype determined brain metabolic profile. Consistent with the brain metabolome, gene and pathway-based RNA-Seq analyses of the hippocampus indicated increased expression of fatty acid/lipid metabolism related genes and pathways in both hAPOE4 males and females. Further, female transcription of fatty acid and amino acids pathways were significantly different from males. MRI based imaging analyses indicated that in multiple white matter tracts, hAPOE4 males and females exhibited lower fractional anisotropy than their hAPOE3 counterparts, suggesting a lower level of white matter integrity in hAPOE4 mice. Consistent with the brain metabolomic and transcriptomic profile of hAPOE4 carriers, beta-amyloid generation was detectable in 16-month-old male and female brains. These data provide therapeutic targets based on chromosomal sex and APOE genotype. Collectively, these data provide a framework for developing precision medicine interventions during the prodromal phase of LOAD, when the potential to reverse, prevent and delay LOAD progression is greatest.
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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 OpenQuestion graph.