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- W4380153722 abstract "Abstract For over a century, brain research narrative has mainly centered on neuron cells. Accordingly, most whole-brain neurodegenerative studies focus on neuronal dysfunction and their selective vulnerability, while we lack comprehensive analyses of other major cell-types’ contribution. By unifying spatial gene expression, structural MRI, and cell deconvolution, here we describe how the human brain distribution of canonical cell-types extensively predicts tissue damage in eleven neurodegenerative disorders, including early- and late-onset Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, amyotrophic lateral sclerosis, frontotemporal dementia, and tauopathies. We reconstructed comprehensive whole-brain reference maps of cellular abundance for six major cell-types and identified characteristic axes of spatial overlapping with atrophy. Our results support the strong mediating role of non-neuronal cells, primarily microglia and astrocytes, on spatial vulnerability to tissue loss in neurodegeneration, with distinct and shared across-disorders pathomechanisms. These observations provide critical insights into the multicellular pathophysiology underlying spatiotemporal advance in neurodegeneration. Notably, they also emphasize the need to exceed the current neuro-centric view of brain diseases, supporting the imperative for cell-specific therapeutic targets in neurodegeneration. One Sentence Summary Major cell-types distinctively associate with spatial vulnerability to tissue loss in eleven neurodegenerative disorders." @default.
- W4380153722 created "2023-06-11" @default.
- W4380153722 creator A5001012430 @default.
- W4380153722 creator A5021783699 @default.
- W4380153722 creator A5038195988 @default.
- W4380153722 creator A5051587217 @default.
- W4380153722 creator A5051732001 @default.
- W4380153722 creator A5082152779 @default.
- W4380153722 date "2023-06-09" @default.
- W4380153722 modified "2023-09-24" @default.
- W4380153722 title "Distinctive Whole-brain Cell-Types Strongly Predict Tissue Damage Patterns in Eleven Neurodegenerative Disorders" @default.
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