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Super-resolved Spatial Transcriptomics Reveals Early Changes In Rna Localization In The 5xfad Hippocampus.

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Super-resolved Spatial Transcriptomics Reveals Early Changes In Rna Localization In The 5xfad Hippocampus.

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Super-Resolved Spatial Transcriptomics Reveals Early Changes in RNA Localization in the 5xFAD Hippocampus.

Yaara Diamant Karasik^1,2,3, Hadar Eger^1,2,3, Tal Goldberg^1,2,3

¹Faculty of Engineering, Bar-Ilan University, Israel.

Biorxiv : the Preprint Server for Biology

|October 3, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Early disruptions in RNA spatial organization, not just expression levels, are key features of Alzheimer's disease (AD) onset. Expansion Sequencing (ExSeq) reveals altered gene positioning in the 5xFAD mouse model before significant pathology develops.

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Area of Science:

Neuroscience
Genomics
Molecular Biology

Background:

Alzheimer's disease (AD) involves cell-type-specific gene expression and RNA localization changes.
Early spatial dysregulation of RNA in neurodegeneration is not well understood.

Purpose of the Study:

To investigate early spatial RNA dysregulation in the hippocampus of a mouse model of AD.
To define changes in RNA spatial organization prior to overt neuropathology.

Main Methods:

Expansion Sequencing (ExSeq) was used to map the spatial distribution of 101 genes.
Analysis was performed on 4-week-old 5xFAD and wild-type (WT) mice.
Spatial RNA velocity analysis was employed to assess cell-type-specific state differences.

Main Results:

Identified 23 genes with altered RNA localization but unchanged abundance in 5xFAD mice.
Discovered early differences in RNA spatial organization independent of overall expression changes.
Detected cell-type- and region-specific transcriptomic state differences linked to cell-cell interactions.

Conclusions:

Disrupted RNA positioning is an early molecular feature of Alzheimer's disease.
ExSeq provides a spatially resolved view of transcriptomic alterations during AD onset.
Early spatial RNA changes may precede overt pathology in AD.