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13.12.2023 | Original Article

Multivariate investigation of aging in mouse models expressing the Alzheimer’s protective APOE2 allele: integrating cognitive metrics, brain imaging, and blood transcriptomics

verfasst von: Hae Sol Moon, Ali Mahzarnia, Jacques Stout, Robert J. Anderson, Madison Strain, Jessica T. Tremblay, Zay Yar Han, Andrei Niculescu, Anna MacFarlane, Jasmine King, Allison Ashley-Koch, Darin Clark, Michael W. Lutz, Alexandra Badea

Erschienen in: Brain Structure and Function | Ausgabe 1/2024

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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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Titel: Multivariate investigation of aging in mouse models expressing the Alzheimer’s protective APOE2 allele: integrating cognitive metrics, brain imaging, and blood transcriptomics
verfasst von: Hae Sol Moon
Ali Mahzarnia
Jacques Stout
Robert J. Anderson
Madison Strain
Jessica T. Tremblay
Zay Yar Han
Andrei Niculescu
Anna MacFarlane
Jasmine King
Allison Ashley-Koch
Darin Clark
Michael W. Lutz
Alexandra Badea
Publikationsdatum: 13.12.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Brain Structure and Function / Ausgabe 1/2024
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-023-02731-x

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Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Update Neurologie

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Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

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Weitere Artikel der Ausgabe 1/2024

Childhood development of brain white matter myelin: a longitudinal T1w/T2w-ratio study

Neonatal olfactory bulbectomy causes dendritic spine retraction in dorsal hippocampal CA3 neurons in female rats and spatial learning deficits in male rats

Relative contribution of lateral vestibular neuron and abducens internuclear neuron inputs to the discharge activity of medial rectus motoneurons

Selective vulnerability of motor neuron types and functional groups to degeneration in amyotrophic lateral sclerosis: review of the neurobiological mechanisms and functional correlates

Should one go for individual- or group-level brain parcellations? A deep-phenotyping benchmark