ArticleBrain structure & function2024
Multivariate investigation of aging in mouse models expressing the Alzheimer's protective APOE2 allele: integrating cognitive metrics, brain imaging, and blood transcriptomics.
Article in Brain structure & function, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- Olfactory-Guided Behavior Uncovers Imaging and Molecular Signatures of Alzheimer's Disease Risk.Brain sciences · 2025Article
- Smelling the Risk: Early Olfactory Deficits, Brain Networks, and Blood Markers of Alzheimer's Disease Risk in Humanized APOE Mice.bioRxiv : the preprint server for biology · 2025Article
- Network biomarkers of Alzheimer's disease risk derived from joint volume and texture covariance patterns in mouse models.PloS one · 2025Article
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14 authors at 1 institution in 1 country.
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Abstract
APOE allelic variation is critical in brain aging and Alzheimer's disease (AD). The APOE2 allele associated with cognitive resilience and neuroprotection against AD remains understudied. We employed a multipronged approach to characterize the transition from middle to old age in mice with APOE2 allele, using behavioral assessments, image-derived morphometry and diffusion metrics, structural connectomics, and blood transcriptomics. We used sparse multiple canonical correlation analyses (SMCCA) for integrative modeling, and graph neural network predictions. Our results revealed brain sub-networks associated with biological traits, cognitive markers, and gene expression. The cingulate cortex emerged as a critical region, demonstrating age-associated atrophy and diffusion changes, with higher fractional anisotropy in males and middle-aged subjects. Somatosensory and olfactory regions were consistently highlighted, indicating age-related atrophy and sex differences. The hippocampus exhibited significant volumetric changes with age, with differences between males and females in CA3 and CA1 regions. SMCCA underscored changes in the cingulate cortex, somatosensory cortex, olfactory regions, and hippocampus in relation to cognition and blood-based gene expression. Our integrative modeling in aging APOE2 carriers revealed a central role for changes in gene pathways involved in localization and the negative regulation of cellular processes. Our results support an important role of the immune system and response to stress. This integrative approach offers novel insights into the complex interplay among brain connectivity, aging, and sex. Our study provides a foundation for understanding the impact of APOE2 allele on brain aging, the potential for detecting associated changes in blood markers, and revealing novel therapeutic intervention targets.
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