Alzheimer’s disease (AD) is the leading cause of dementia in elderly individuals worldwide; however, all the mechanisms leading to its onset and progression are not fully understood. Here, we report single-cell multiome and spatial transcriptomics analysis of the brain in a transgenic rat model of human-like tauopathy. In this advanced transgenic model, we have identified new markers of a tau-driven AD pathology and provided single-cell evidence for previously known genes implicated in AD. Our findings reveal how tau pathological 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 consequence of the tauopathy. Overall, this study reinforces the concept of synaptic dysfunction as a hallmark of AD and highlights potential targets for future mechanistic investigations or novel therapeutic strategies.
from sddb import Catalog
cohort = Catalog().collection("geo-gse305314")
cohort.members # the 4 datasets as a table
print(cohort.licenses()) # check the terms before you download
sdatas = cohort.to_dict() # {uid: SpatialData}, cached locally
# or keep the .zarr files in a folder of your choice:
# sdatas = cohort.to_dict(dest="data/")Needs pip install lamindb and network access to the Lamin database, which is limited during the alpha. If it fails, use the Client tab.
import lamindb as ln
db = ln.DB("scverse/spatialdata-db")
coll = db.Collection.get(key="geo-gse305314")
coll.ordered_artifacts.to_dataframe() # the 4 members, ordered
# download every member .zarr to the local cache:
paths = [a.cache() for a in coll.ordered_artifacts.all()]# sddb client: download every member .zarr into data/
sddb-cli download --collection geo-gse305314 --dest data/Licenses: 4 NCBI GEO policy
@article{Ji_2025,
title = {Intercellular signaling and synaptic deconstruction uncovered by single-cell and spatial transcriptomics in an AD tauopathy model},
volume = {8},
ISSN = {2399-3642},
url = {http://dx.doi.org/10.1038/s42003-025-08959-z},
DOI = {10.1038/s42003-025-08959-z},
number = {1},
journal = {Communications Biology},
publisher = {Springer Science and Business Media LLC},
author = {Ji, Jeff X. and Giles, Brian L. and Bhattacharjee, Surjyadipta and Kautzmann, Marie-Audrey I. and P. Masson, Alasdair and Do Carmo, Sonia and Cuello, A. Claudio and Bazan, Nicolas G.},
year = {2025},
month = Nov
}