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Changes in the primary cilia in Alzheimer’s disease early development is associated with alterations in the axon initial segment.

GSE248779 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/03/13 Platform GPL24247
Summary
Many pathological alterations happen decades before cognitive decline in Alzheimer’s disease (AD) patients. Identifying the earliest changes in AD neurons is crucial for AD diagnosis and therapy development targeting upstream events in AD pathogenesis. Here, we demonstrated the early common alterations in the hippocampal neurons from 3 familial AD mouse lines (APP/PS1, 5FAD, 3*Tg) are associated with the primary cilium morphology and ciliary GPCRs. The primary cilia interact with the axon initial segment (AIS) through ciliary GPCR signaling and transcriptional regulation of AIS mater organizer protein AnkG. Our results provide new insights for AD pathogenesis especially during early stage, and a novel mechanism by which ciliary signaling may modulate neuronal activity through regulating the structure and plasticity of the AIS. Understanding AD development at early stage could help identifying new potential targets for AD prevention and therapy.
Published in
The Primary Cilia are Associated with the Axon Initial Segment in Neurons
Wang H, Li Y, Li X et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2025 · PMID 39804991 · doi:10.1002/advs.202407405
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Also filed as BioProject PRJNA1045993 and SRA study SRP474798. Searching any of these in the dataset finder brings you back here.

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