ArticleNature communications2024
Spatial transcriptomics reveals molecular dysfunction associated with cortical Lewy pathology.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 68 citations in OpenAlex.
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Gray Matter Microstructure Measured Using Diffusion Imaging as a Biomarker of Severity in Lewy Body Diseases.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Epigenetic Mechanisms Underlying Cognitive Dysfunction in Parkinson's Disease: Current Evidence and Future Prospects.Brain and behavior · 2026Review
- Spatial multi-omics identifies early synaptic pruning and context-specific dopaminergic vulnerability in synucleinopathies.Nature communications · 2026Article
- The applications of single-cell and spatial transcriptomics in neuroscience and brain disorders.Neuroscience and biobehavioral reviews · 2026Review
- Knockout of Rab27b exacerbates neuropathology in alpha-synuclein mouse models.Acta neuropathologica communications · 2026Article
- Developmental neurotoxicity of thyroid hormone system-disrupting chemicals: a systems-level exploration using multi-omics approach.Archives of toxicology · 2026Article
- Decoding neurodegeneration one cell at a time.The Journal of clinical investigation · 2026Review
- Massive-scale single-nucleus multi-omics identifies novel rare noncoding drivers of Parkinson's disease.bioRxiv : the preprint server for biology · 2026Article
- Exploring the human brain: spatial transcriptomics challenges and approaches in post-mortem analysis.Brain : a journal of neurology · 2026Review
- Mapping cellular vulnerability in Parkinson's disease using retro-AAVs and preformed α-synuclein fibrils.Translational neurodegeneration · 2026Article
- Spatially resolved molecular signatures of Lewy body dementia.Acta neuropathologica · 2026Article
- In vivo Proximity & Spatial Proteomics with CRISPR Screening Identify STXBP1 as a Protective Modifier of α-synuclein Toxicity in Dopamine Neurons.bioRxiv : the preprint server for biology · 2026Article
- Human Neocortical Glutamatergic Neurons Revealed Through Multimodal Profiling.bioRxiv : the preprint server for biology · 2026Article
- Imaging spatial transcriptomics reveals molecular patterns underlying accumulation of p-Ser129 α-synuclein in a transgenic mouse model.NPJ Parkinson's disease · 2026Article
- Parkinson's disease: spatiotemporal regulation and therapeutic prospects of TREM2-mediated microglial responses.NPJ Parkinson's disease · 2026Review
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Mapping safety in space: the emerging role of spatial transcriptomics in safe drug development.Frontiers in toxicology · 2026Review
- Decoding the brain's ATG8 paralog code: LC3-GABARAP specialization at synapses and the astrocyte-neuron interface.Frontiers in cell and developmental biology · 2026Review
- The extent of alpha-synuclein aggregate accumulation in neurons varies depending on the type of neurotransmitter they release.Scientific reports · 2025Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
A key hallmark of Parkinson's disease (PD) is Lewy pathology. Composed of α-synuclein, Lewy pathology is found both in dopaminergic neurons that modulate motor function, and cortical regions that control cognitive function. Recent work has established the molecular identity of dopaminergic neurons susceptible to death, but little is known about cortical neurons susceptible to Lewy pathology or molecular changes induced by aggregates. In the current study, we use spatial transcriptomics to capture whole transcriptome signatures from cortical neurons with α-synuclein pathology compared to neurons without pathology. We find, both in PD and related PD dementia, dementia with Lewy bodies and in the pre-formed fibril α-synucleinopathy mouse model, that specific classes of excitatory neurons are vulnerable to developing Lewy pathology. Further, we identify conserved gene expression changes in aggregate-bearing neurons that we designate the Lewy-associated molecular dysfunction from aggregates (LAMDA) signature. Neurons with aggregates downregulate synaptic, mitochondrial, ubiquitin-proteasome, endo-lysosomal, and cytoskeletal genes and upregulate DNA repair and complement/cytokine genes. Our results identify neurons vulnerable to Lewy pathology in the PD cortex and describe a conserved signature of molecular dysfunction in both mice and humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.