What it is
The authors used donated brain tissue from 1,494 people to build a population-scale single-cell transcriptomic atlas of the human dorsolateral prefrontal cortex, covering more than 6.3 million individual nuclei from neurotypical controls and from people with eight common brain disorders, among them Alzheimer's disease, Parkinson's disease, schizophrenia and bipolar disorder. Differences between individuals accounted for a substantial share of gene expression variation, and the disorders shared signatures in basic cellular functions such as mRNA processing and protein localization. With those shared signatures set aside, Alzheimer's disease, diffuse Lewy body disease, vascular dementia and Parkinson's disease showed stronger genetic and transcriptomic concordance with one another.
Why it matters
Neurodegenerative and neuropsychiatric diseases impose a considerable public health burden, yet the molecular mechanisms behind them remain poorly understood. Comparing eight disorders in one very large cohort at single-cell resolution sheds light on processes the diseases share and processes that are distinct. Within Alzheimer's disease, more severe cases showed fewer neurons alongside more immune and vascular cells, a pattern distinct from healthy ageing, and the neuropsychiatric symptoms that often accompany Alzheimer's were associated with more deep-layer excitatory neurons.
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Filed underSingle-cell and spatial transcriptomics, Neuroinflammation and Neurodegeneration Mechanisms, Tryptophan and brain disorders