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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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Wartezeit nicht kürzer, aber Arbeit flexibler

Psychotherapie Medizin aktuell

Fünf Jahren nach der Neugestaltung der Psychotherapie-Richtlinie wurden jetzt die Effekte der vorgenommenen Änderungen ausgewertet. Das Hauptziel der Novellierung war eine kürzere Wartezeit auf Therapieplätze. Dieses Ziel wurde nicht erreicht, es gab jedoch positive Auswirkungen auf andere Bereiche.

Update Neurologie

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Springer Medizin

Abstract

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Weitere Artikel der Ausgabe 1/2024

Neuroanatomical correlates of aggressiveness: a case–control voxel- and surface-based morphometric study

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

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

Altered functional brain networks in coronary heart disease: independent component analysis and graph theoretical analysis

ProbaStem, a pipeline towards the first high-resolution probabilistic atlas of the whole human brainstem