Video Experimental Relacionado

Updated: Jan 8, 2026

Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses

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Ciencia básica y patogénesis

¹Korea Advanced Institute of Science and Technology, Yuseong-gu, Daejeon, Korea, Republic of (South).

Alzheimer's & dementia : the journal of the Alzheimer's Association

|December 24, 2025

Abstracto

Background:

Synucleinopathies and Alzheimer's disease (AD) share both common and distinct molecular and pathological features, but a comprehensive characterization of these diseases remains elusive.

Methods:

We constructed a single-nucleus and spatial transcriptome atlas of synucleinopathies and AD, analyzing 3.4 million nuclei from 513 post-mortem human brain samples. Using 167 transcriptomic meta-programs, we elucidated the complex molecular mechanisms underlying both diseases. We also examined co-dysregulated meta-programs across different cell types in each patient.

Results:

Notably, we identified 44 disease-specific meta-programs, including inflammatory responses in microglia, across synucleinopathies and AD. We further revealed co-dysregulation of microglia and oligodendrocyte precursor cells (OPCs) in AD. In contrast, synucleinopathies demonstrated co-dysregulation of astrocytes, microglia, and vascular cells. These co-dysregulated transcriptomic meta-programs were verified by spatial transcriptomics using MERFISH.

Conclusion:

Our integrative analysis of single-cell and spatial transcriptomes provides insights into the shared and unique molecular signatures underlying neurodegenerative diseases.

Palabras clave:

sinucleinopatías enfermedad de Alzheimer transcriptómica células cerebrales enfermedades neurodegenerativas

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