ArticleNature neuroscience2022
Neurovascular dysfunction in GRN-associated frontotemporal dementia identified by single-nucleus RNA sequencing of human cerebral cortex.
Article in Nature neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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57 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Brain DNA methylomic analysis of frontotemporal lobar degeneration reveals OTUD4 in shared dysregulated signatures across pathological subtypes.Acta neuropathologica · 2023Pooled it
- Distinct proteomic CSF profiles in genetic frontotemporal lobar degeneration.Brain : a journal of neurology · 2026Article
- Article
- Progranulin haploinsufficiency remodels the cerebral microvasculature and neurovascular unit.bioRxiv : the preprint server for biology · 2026Article
- TGF-β signaling promotes astroglial activation and TDP-43 proteinopathy in organoid models of frontotemporal lobar degeneration.The Journal of clinical investigation · 2026Article
- Shared and disease-specific human brain vascular signatures in Alzheimer's disease, frontotemporal dementia, and Huntington's disease.bioRxiv : the preprint server for biology · 2026Article
- Progranulin deficiency induces premature vascular senescence and dysfunction.American journal of physiology. Heart and circulatory physiology · 2026Article
- Transcriptional analyses identify pericyte-centered signaling programs altered by sex and brain region in Alzheimer's Disease.Communications biology · 2026Article
- Single-nucleus multiomic atlas of ALS primary motor cortex nominates neuroprotective WDR49-expressing astrocytes.Research square · 2026Article
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- Single-nucleus RNA sequencing reveals GABAergic vulnerability and reactive gliosis driven by loss of TDP-43.iScience · 2025Article
- Delivering Progranulin to Astrocytic Lysosomes Promotes Growth of Co-Cultured Neurons.Journal of neurochemistry · 2025Article
- C9orf72 hexanucleotide repeat expansions impair microglial response in ALS.Nature neuroscience · 2025Article
- Disrupted Coupling Between Cerebral Glucose Metabolism and Intrinsic Functional Connectivity: A Hybrid PET/fMRI Study on Frontotemporal Dementia.Human brain mapping · 2025Article
- Ablation of progranulin augments microglial activation and accelerates prion progression.Acta neuropathologica communications · 2025Article
- Integrative analysis reveals generalizable human neurodegenerative disease-associated glial states.bioRxiv : the preprint server for biology · 2025Article
- Cerebrovascular Reactivity at Rest and Its Association With Cognitive Function in People With Genetic Frontotemporal Dementia.Neurology · 2025Article
- Glymphatic activity in behavioral variant frontotemporal dementia: Link with vascular function and astrocytic activation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Disruption of the cerebrospinal fluid-plasma protein balance in cognitive impairment and aging.Nature medicine · 2025Article
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Frontotemporal dementia (FTD) is the second most prevalent form of early-onset dementia, affecting predominantly frontal and temporal cerebral lobes. Heterozygous mutations in the progranulin gene (GRN) cause autosomal-dominant FTD (FTD-GRN), associated with TDP-43 inclusions, neuronal loss, axonal degeneration and gliosis, but FTD-GRN pathogenesis is largely unresolved. Here we report single-nucleus RNA sequencing of microglia, astrocytes and the neurovasculature from frontal, temporal and occipital cortical tissue from control and FTD-GRN brains. We show that fibroblast and mesenchymal cell numbers were enriched in FTD-GRN, and we identified disease-associated subtypes of astrocytes and endothelial cells. Expression of gene modules associated with blood-brain barrier (BBB) dysfunction was significantly enriched in FTD-GRN endothelial cells. The vasculature supportive function and capillary coverage by pericytes was reduced in FTD-GRN tissue, with increased and hypertrophic vascularization and an enrichment of perivascular T cells. Our results indicate a perturbed BBB and suggest that the neurovascular unit is severely affected in FTD-GRN.
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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.