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Intercellular signaling and synaptic deconstruction uncovered by single-cell and spatial transcriptomics in an AD
Jeff X Ji1, Brian L Giles1, Surjyadipta Bhattacharjee1
1Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA, 70112, USA.
Communications Biology
|November 18, 2025
Summary
This study identifies new Alzheimer's disease (AD) markers and reveals how tau pathology and aging impact brain cell communication. Findings highlight synaptic dysfunction as an early event, suggesting potential therapeutic targets for AD.
Area of Science:
- Neuroscience
- Genomics
- Molecular Biology
Background:
- Alzheimer's disease (AD) is the primary cause of dementia in older adults globally.
- The precise mechanisms driving AD onset and progression remain incompletely understood.
- Tauopathy, characterized by tau protein abnormalities, is a key pathological feature in AD.
Purpose of the Study:
- To investigate the molecular mechanisms of tau-driven Alzheimer's disease pathology.
- To identify novel biomarkers for tau-driven AD.
- To explore the impact of tau hyperphosphorylation and aging on cellular networks and communication in the brain.
Main Methods:
- Utilized single-cell multiome and spatial transcriptomics.
- Employed a transgenic rat model exhibiting human-like tauopathy.
- Analyzed alterations in ligand-receptor interactions, transcription factor networks, and cellular communication pathways.
Main Results:
- Identified novel markers associated with tau-driven AD pathology.
- Provided single-cell resolution evidence for genes implicated in AD.
- Revealed significant changes in cell communication, including glutamatergic transmission and Netrin signaling, as consequences of tauopathy.
- Demonstrated how tau hyperphosphorylation and aging affect regulatory networks and cellular interactions.
Conclusions:
- Synaptic dysfunction is a critical early event in Alzheimer's disease.
- Tau pathology significantly alters brain cell communication and regulatory networks.
- The study highlights potential novel therapeutic targets for AD treatment.
