Document Type
Article
Publication Date
11-17-2025
Publication Title
Communications Biology
Abstract
Alzheimer's disease (AD) is the leading cause of dementia in elderly individuals worldwide; however, all mechanisms leading to disease onset and progression are not well understood. Here, we report brain single-cell multiome and spatial transcriptomics in a transgenic rat model of human-like tauopathy. We have identified new markers of tau-driven AD pathology and provided single-cell evidence for genes implicated in AD. Our findings reveal how tau hyperphosphorylation and aging alter ligand-receptor communication, transcription factor regulatory networks, and specific cellular networks. Notably, we found intriguing changes in cell communication involving glutamatergic transmission and Netrin signaling as a taupathy consequence. Overall, this study reinforces the concept that synaptic dysfunction is a critical early event in AD and highlights potential targets as potential therapeutic strategies.
First Page
1
Last Page
19
PubMed ID
41249845
Volume
8
Issue
1
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Ji, Jeff X.; Giles, Brian L.; Bhattacharjee, Surjyadipta; Kautzmann, Marie-Audrey I.; Masson, Alasdair P.; Do Carmo, Sonia; Cuello, A Claudio; and Bazan, Nicolas G., "Intercellular signaling and synaptic deconstruction uncovered by single-cell and spatial transcriptomics in an AD tauopathy model" (2025). School of Medicine Faculty Publications. 4386.
https://digitalscholar.lsuhsc.edu/som_facpubs/4386
10.1038/s42003-025-08959-z
Included in
Amino Acids, Peptides, and Proteins Commons, Investigative Techniques Commons, Nervous System Diseases Commons