ArticleActa neuropathologica communications2022
Distinct cell type-specific protein signatures in GRN and MAPT genetic subtypes of frontotemporal dementia.
Article in Acta neuropathologica communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Pooled it
- Genetic frontotemporal degeneration across the lifespan? A critical appraisal of the neurodevelopmental hypothesis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Using iPSC models to examine neuron-glia interactions in neurodegenerative diseases.Bioscience reports · 2026Review
- Progranulin deficiency in the brain activates an insulin signaling pathway that may promote neurodegeneration.iScience · 2026Article
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- Decoding Dementia Mechanisms: Identification of Key Oligodendrocyte- Associated Genes through Integrative Bioinformatics and Machine Learning.Current topics in medicinal chemistry · 2026Article
- One-step induction of human GABAergic neurons promotes presynaptic development & synapse maturation.bioRxiv : the preprint server for biology · 2025Article
- Large-scale CSF proteome profiling identifies biomarkers for accurate diagnosis of frontotemporal dementia.Molecular neurodegeneration · 2025Article
- Proteomics of the temporal cortex in semantic dementia reveals brain-region specific molecular pathology and regulation of the TDP-43-ANXA11 interactome.Acta neuropathologica communications · 2025Article
- Article
- Integrated View of Baseline Protein Expression in Human Tissues Using Public Data Independent Acquisition Data Sets.Journal of proteome research · 2025Article
- The Underestimated Role of Iron in Frontotemporal Dementia: A Narrative Review.International journal of molecular sciences · 2024Review
- A Human Brain-Chip for Modeling Brain Pathologies and Screening Blood-Brain Barrier Crossing Therapeutic Strategies.Pharmaceutics · 2024Article
- Proteomic networks of gray and white matter reveal tissue-specific changes in human tauopathy.Annals of clinical and translational neurology · 2024Article
- Behavioral variant frontotemporal dementia associated with GRN and ErbB4 gene mutations: a case report and literature review.BMC medical genomics · 2024Review
- Multi-modal proteomic characterization of lysosomal function and proteostasis in progranulin-deficient neurons.Molecular neurodegeneration · 2023Article
- CSF proteomics in autosomal dominant Alzheimer's disease highlights parallels with sporadic disease.Brain : a journal of neurology · 2023Article
- Astrocytes: Dissecting Their Diverse Roles in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Cells · 2023Review
- Clusters of co-abundant proteins in the brain cortex associated with fronto-temporal lobar degeneration.Alzheimer's research & therapy · 2023Article
- Proteomics of the dentate gyrus reveals semantic dementia specific molecular pathology.Acta neuropathologica communications · 2022Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Frontotemporal dementia is characterized by progressive atrophy of frontal and/or temporal cortices at an early age of onset. The disorder shows considerable clinical, pathological, and genetic heterogeneity. Here we investigated the proteomic signatures of frontal and temporal cortex from brains with frontotemporal dementia due to GRN and MAPT mutations to identify the key cell types and molecular pathways in their pathophysiology. We compared patients with mutations in the GRN gene (n = 9) or with mutations in the MAPT gene (n = 13) with non-demented controls (n = 11). Using quantitative proteomic analysis on laser-dissected tissues we identified brain region-specific protein signatures for both genetic subtypes. Using published single cell RNA expression data resources we deduced the involvement of major brain cell types in driving these different protein signatures. Subsequent gene ontology analysis identified distinct genetic subtype- and cell type-specific biological processes. For the GRN subtype, we observed a distinct role for immune processes related to endothelial cells and for mitochondrial dysregulation in neurons. For the MAPT subtype, we observed distinct involvement of dysregulated RNA processing, oligodendrocyte dysfunction, and axonal impairments. Comparison with an in-house protein signature of Alzheimer's disease brains indicated that the observed alterations in RNA processing and oligodendrocyte function are distinct for the frontotemporal dementia MAPT subtype. Taken together, our results indicate the involvement of different brain cell types and biological mechanisms in genetic subtypes of frontotemporal dementia. Furthermore, we demonstrate that comparison of proteomic profiles of different disease entities can separate general neurodegenerative processes from disease-specific pathways, which may aid the development of disease subtype-specific treatment strategies.
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