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Publication : Brain regions differences in amyloid-β and gene expression in early APP/PS1 mice and identification of Npas4 as a key molecule in Alzheimer's disease.

First Author  Wang N Year  2024
Journal  Biomol Biomed Volume  24
Issue  6 Pages  1816-1826
PubMed ID  38958450 Mgi Jnum  J:360715
Mgi Id  MGI:7787202 Doi  10.17305/bb.2024.10820
Citation  Wang N, et al. (2024) Brain regions differences in amyloid-beta and gene expression in early APP/PS1 mice and identification of Npas4 as a key molecule in Alzheimer's disease. Biomol Biomed 24(6):1816-1826
abstractText  Distinct brain regions are differentially affected during the various stages of Alzheimer's disease (AD). While the hippocampus and cortex are known to play significant roles, the involvement of the cerebellum has received less attention. Understanding the changes in diverse brain regions is essential to unravel the neuropathological mechanism in early-stage AD. Our research aimed to explore and compare amyloid-beta (Abeta) pathology and gene expression profiles across the hippocampus, cortex, and cerebellum in the early stages of the Amyloid Precursor Protein/Presenilin-1 (APP/PS1) mouse model. By 7 months of age, significant Abeta plaque accumulation was observed in the hippocampus and cortex of APP/PS1 mice, while no such deposits were found in the cerebellum. Gene expression analysis revealed predominant effects on immune response pathways in the hippocampus and cortex. Even in the absence of Abeta deposition, notable gene expression changes were observed in the cerebellum of APP/PS1 mice. Intriguingly, Neuronal PAS Domain protein 4 (Npas4) expression was consistently down-regulated across all brain regions, independent of Abeta plaque presence. Our findings reveal distinct transcriptomic alterations and Abeta pathology in select cerebral regions during the initial phase of AD. Notably, the diminished expression of the Npas4 across three brain regions implies that Npas4 could play a pivotal role in the early pathogenesis of AD.
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