ArticleActa neuropathologica2019
Neurons selectively targeted in frontotemporal dementia reveal early stage TDP-43 pathobiology.
Article in Acta neuropathologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.
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Who cites it
94 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Survival and Prognostic Factors in C9orf72 Repeat Expansion Carriers: A Systematic Review and Meta-analysis.JAMA neurology · 2020Pooled it
- An atlas of primate insular cortex reveals a signal-processing strategy in von Economo neurons.Nature cell biology · 2026Article
- Single-cell transcriptomic atlas of frontoinsular cortex reveals molecular correlates of selective neuronal vulnerability in FTD.bioRxiv : the preprint server for biology · 2026Article
- TAF15 amyloids propagate via defined motifs in a prion-like fashion.Nature communications · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- Dynamic thermodynamic-informational entropic relationship (TIER) models of selective vulnerability to neurodegeneration.bioRxiv : the preprint server for biology · 2026Article
- Frontotemporal dementia patient-derived iPSC neurons show cell pathological hallmarks and evidence for synaptic dysfunction and DNA damage.Molecular psychiatry · 2026Article
- Statins and genetic inhibition of the mevalonate pathway activate an ATF3-STMN2 regenerative program.bioRxiv : the preprint server for biology · 2026Article
- Vulnerability of anterior cingulate Von Economo neurons to FTLD-tauopathies in behavioral variant frontotemporal dementia.Cerebral cortex (New York, N.Y. : 1991) · 2026Article
- TDP-43 dysfunction leads to the accumulation of cryptic transposable element-derived exons, crypTEs, in iPSC derived neurons and ALS/FTD patient tissues.bioRxiv : the preprint server for biology · 2026Article
- Functional network collapse in neurodegenerative disease.Nature communications · 2025Article
- A single-cell, long-read, isoform-resolved case-control study of FTD reveals cell-type-specific and broad splicing dysregulation in human brain.Cell reports · 2025Article
- Article
- Cryptic splicing in synaptic and membrane excitability genes links TDP-43 loss to neuronal dysfunction.bioRxiv : the preprint server for biology · 2025Article
- Broad brain biodistribution conferred by an AAV to restore TDP-43 function mitigates Frontotemporal Demenia-like deficits.bioRxiv : the preprint server for biology · 2025Article
- Symptomatic treatment by a BBB-permeable AAV engineered to restore TDP-43 function slows motor neuron disease and prevents paralysis.bioRxiv : the preprint server for biology · 2025Article
- Sporadic ALS induced pluripotent stem cell derived neurons reveal hallmarks of TDP-43 loss of function.Nature communications · 2025Article
- Synapse vulnerability and resilience across the clinical spectrum of dementias.Nature reviews. Neurology · 2025Review
- Maintenance of neuronal TDP-43 expression requires axonal lysosome transport.bioRxiv : the preprint server for biology · 2025Article
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
34 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 2 institutions in 2 countries.
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Abstract
TAR DNA-binding protein 43 (TDP-43) aggregation is the most common pathological hallmark in frontotemporal dementia (FTD) and characterizes nearly all patients with motor neuron disease (MND). The earliest stages of TDP-43 pathobiology are not well-characterized, and whether neurodegeneration results from TDP-43 loss-of-function or aggregation remains unclear. In the behavioral variant of FTD (bvFTD), patients undergo selective dropout of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices. Here, we examined TDP-43 pathobiology within these vulnerable neurons in the FI across a clinical spectrum including 17 patients with sporadic bvFTD, MND, or both. In an exploratory analysis based on our initial observations, we further assessed ten patients with C9orf72-associated bvFTD/MND. VENs and fork cells showed early, disproportionate TDP-43 aggregation that correlated with anatomical and clinical severity, including loss of emotional empathy. The presence of a TDP-43 inclusion was associated with striking nuclear and somatodendritic atrophy. An intriguing minority of neurons lacked detectable nuclear TDP-43 despite the apparent absence of a cytoplasmic TDP-43 inclusion. These cells showed neuronal atrophy comparable to inclusion-bearing neurons, suggesting that the loss of nuclear TDP-43 function promotes neurodegeneration, even when TDP-43 aggregation is inconspicuous or absent.
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