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Basic Science and Pathogenesis.

Inkyung Jung1

  • 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
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Summary
This summary is machine-generated.

This study reveals unique molecular signatures in synucleinopathies and Alzheimer's disease (AD) by analyzing brain cell transcriptomes. It highlights distinct cell type co-dysregulation patterns in these neurodegenerative diseases.

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Area of Science:

  • Neurobiology
  • Genomics
  • Pathology

Background:

  • Synucleinopathies and Alzheimer's disease (AD) share molecular and pathological features, necessitating deeper characterization.
  • Understanding shared and distinct disease mechanisms is crucial for neurodegenerative disease research.

Purpose of the Study:

  • To create a comprehensive transcriptomic atlas of synucleinopathies and AD.
  • To identify and compare molecular mechanisms and cell type co-dysregulation in these diseases.

Main Methods:

  • Constructed a single-nucleus and spatial transcriptome atlas from 513 post-mortem human brain samples.
  • Analyzed 3.4 million nuclei using 167 transcriptomic meta-programs.
  • Verified findings using MERFISH spatial transcriptomics.

Main Results:

  • Identified 44 disease-specific meta-programs, including microglial inflammatory responses.
  • Revealed co-dysregulation of microglia and oligodendrocyte precursor cells (OPCs) in AD.
  • Found co-dysregulation of astrocytes, microglia, and vascular cells in synucleinopathies.

Conclusions:

  • Integrative analysis of single-cell and spatial transcriptomes offers insights into neurodegenerative disease signatures.
  • Identified shared and unique molecular pathways differentiating synucleinopathies and AD.