Temporal Alterations in White Matter in An App Knock-In Mouse Model of Alzheimer's Disease.

Autor:	Morrissey ZD; Graduate Program in Neuroscience, University of Illinois Chicago, Chicago, Illinois 60612.; Department of Psychiatry, University of Illinois Chicago, Chicago, Illinois 60612.; Department of Anatomy & Cell Biology, University of Illinois Chicago, Chicago, Illinois 60612., Gao J; Department of Electrical & Computer Engineering, University of Illinois Chicago, Chicago, Illinois 60607.; Preclinical Imaging Core, University of Illinois Chicago, Chicago, Illinois 60612., Shetti A; Department of Anatomy & Cell Biology, University of Illinois Chicago, Chicago, Illinois 60612., Li W; Department of Chemistry, University of Illinois Chicago, Chicago, Illinois 60607., Zhan L; Department of Electrical & Computer Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261., Li W; Preclinical Imaging Core, University of Illinois Chicago, Chicago, Illinois 60612.; Department of Bioengineering, University of Illinois Chicago, Chicago, Illinois 60607.; Department of Radiology, Northwestern University, Chicago, Illinois 60611., Fortel I; Department of Bioengineering, University of Illinois Chicago, Chicago, Illinois 60607., Saido T; Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Wako 351-0198, Japan., Saito T; Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University, Nagoya 467-8601, Japan., Ajilore O; Department of Psychiatry, University of Illinois Chicago, Chicago, Illinois 60612., Cologna SM; Department of Chemistry, University of Illinois Chicago, Chicago, Illinois 60607., Lazarov O; Department of Anatomy & Cell Biology, University of Illinois Chicago, Chicago, Illinois 60612 olazarov@uic.edu., Leow AD; Department of Psychiatry, University of Illinois Chicago, Chicago, Illinois 60612.; Department of Bioengineering, University of Illinois Chicago, Chicago, Illinois 60607.; Department of Computer Science, University of Illinois Chicago, Chicago, Illinois 60607.
Jazyk:	angličtina
Zdroj:	ENeuro [eNeuro] 2024 Feb 26; Vol. 11 (2). Date of Electronic Publication: 2024 Feb 26 (Print Publication: 2024).
DOI:	10.1523/ENEURO.0496-23.2024
Abstrakt:	Alzheimer's disease (AD) is the most common form of dementia and results in neurodegeneration and cognitive impairment. White matter (WM) is affected in AD and has implications for neural circuitry and cognitive function. The trajectory of these changes across age, however, is still not well understood, especially at earlier stages in life. To address this, we used the App NL-G-F/NL-G-F knock-in (APPKI) mouse model that harbors a single copy knock-in of the human amyloid precursor protein ( APP ) gene with three familial AD mutations. We performed in vivo diffusion tensor imaging (DTI) to study how the structural properties of the brain change across age in the context of AD. In late age APPKI mice, we observed reduced fractional anisotropy (FA), a proxy of WM integrity, in multiple brain regions, including the hippocampus, anterior commissure (AC), neocortex, and hypothalamus. At the cellular level, we observed greater numbers of oligodendrocytes in middle age (prior to observations in DTI) in both the AC, a major interhemispheric WM tract, and the hippocampus, which is involved in memory and heavily affected in AD, prior to observations in DTI. Proteomics analysis of the hippocampus also revealed altered expression of oligodendrocyte-related proteins with age and in APPKI mice. Together, these results help to improve our understanding of the development of AD pathology with age, and imply that middle age may be an important temporal window for potential therapeutic intervention. Competing Interests: The authors declare no competing financial interests. (Copyright © 2024 Morrissey et al.)
Databáze:	MEDLINE
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