ArticleFrontiers in neuroscience2026
Humanized APOE mouse brain volume increases over age irrespective of sex and APOE genotype: implications for translational validity to the human.
Article in Frontiers in neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Humanized APOE mouse models are widely used to study late-onset Alzheimer's disease (LOAD) risk, yet it remains unclear whether they reproduce the macrostructural brain changes observed in human aging and disease. Methods: We performed Results: Total brain volume increased with age (cross-sectional estimate: 2.12 mm Conclusion: These findings indicate that, despite incorporating a major genetic risk factor for LOAD, this model does not reproduce the atrophy phenotype characteristic of human aging and Alzheimer's disease. Instead, the observed pattern is more consistent with non-pathological or vulnerable aging, suggesting that humanized APOE alone is insufficient to induce MRI-detectable macrostructural atrophy within this cross-sectional comparison, though this finding does not preclude other APOE-dependent pathological mechanisms.
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