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Basic Science and Pathogenesis.

Donghoon Lee1

  • 1Icahn School of Medicine at Mount Sinai, New York, NY, USA.

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This summary is machine-generated.

This study created a large single-cell atlas of the human brain, revealing shared molecular changes in neurodegenerative diseases like Alzheimer's and Parkinson's, and identifying potential therapeutic targets.

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Area of Science:

  • Neuroscience
  • Genomics
  • Molecular Biology

Background:

  • Neurodegenerative and neuropsychiatric diseases present a significant public health challenge.
  • Understanding the molecular underpinnings of these complex brain disorders is limited.

Purpose of the Study:

  • To generate a population-scale single-cell transcriptomic atlas of the human dorsolateral prefrontal cortex (DLPFC).
  • To gain deeper insights into the etiology of various brain diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and schizophrenia.

Main Methods:

  • Generated a single-cell transcriptomic atlas from 1,494 unique donors, comprising over 6.3 million nuclei.
  • Analyzed transcriptomic variation across neurotypical controls and individuals with eight common brain disorders.

Main Results:

  • Identified substantial inter-individual gene expression variation in the DLPFC.
  • Revealed universal transcriptomic signatures related to basic cellular functions across diseases.
  • Demonstrated strong genetic and transcriptomic concordance among AD, diffuse Lewy body disease (DLBD), vascular dementia (Vas), and PD, linked to altered neuronal synaptic signaling.
  • Characterized AD-specific transcriptomic variations, highlighting roles of interneurons, immune, and vascular cells, and identified links to deep layer excitatory neurons.

Conclusions:

  • The developed atlas offers a novel perspective on the transcriptomic landscape of neurodegenerative and neuropsychiatric diseases.
  • Shed light on shared and distinct molecular processes involving neuro-immune-vascular systems.
  • Identified potential therapeutic targets for brain disorders.