ArticleDisease models & mechanisms2022
TDP-43 promotes tau accumulation and selective neurotoxicity in bigenic Caenorhabditis elegans.
Article in Disease models & mechanisms, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- TDP-43 dysfunction facilitates the pathological conversion of tau.Molecular neurodegeneration · 2026Article
- Riboregulation: a non-canonical tau function.Molecular neurodegeneration · 2026Review
- Dominant α-tubulin mutations rescue tauopathy neurodegenerative phenotypes inbioRxiv : the preprint server for biology · 2026Article
- A Robust Chemical-free Platform for Age-SynchronizedbioRxiv : the preprint server for biology · 2026Article
- Glutamatergic neuron degeneration inmicroPublication biology · 2026Article
- TDP-43 proteinopathies and neurodegeneration: insights from Caenorhabditis elegans models.The FEBS journal · 2026Review
- Tau protein: Physiological functions and multifaceted roles in neurodegenerative and psychiatric disorders.Genomic psychiatry : advancing science from genes to society · 2025Article
- Direct interaction between TDP-43 and Tau promotes their co-condensation, while suppressing Tau fibril formation and seeding.The EMBO journal · 2025Article
- Increased Incidence of Epilepsy in a Brain Bank Alzheimer's Disease Cohort and Its Association With TDP-43 Pathology.Neuropathology and applied neurobiology · 2025Article
- Alzheimer's disease neuropathology and its estimation with fluid and imaging biomarkers.Molecular neurodegeneration · 2025Review
- Recent Advances in Co-Condensation and Co-Aggregation of Amyloid Proteins Linked to Neurodegenerative Diseases.Current protein & peptide science · 2025Review
- Expression of polyglutamine repeats at the pathogenic threshold modestly enhances tau neurotoxicity and protein accumulation inmicroPublication biology · 2025Article
- Decreased Hsp90 activity protects against TDP-43 neurotoxicity in a C. elegans model of amyotrophic lateral sclerosis.PLoS genetics · 2024Article
- Co-Aggregation of TDP-43 with Other Pathogenic Proteins and Their Co-Pathologies in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Potential Mechanisms of Tunneling Nanotube Formation and Their Role in Pathology Spread in Alzheimer's Disease and Other Proteinopathies.International journal of molecular sciences · 2024Review
- Grey matter ageing-related tau astrogliopathy: associations with brain pathologies and cognitive decline.Brain : a journal of neurology · 2024Article
- Endoplasmic reticulum unfolded protein response transcriptional targets of XBP-1s mediate rescue from tauopathy.Communications biology · 2024Article
- Depletion of TDP-43 exacerbates tauopathy-dependent brain atrophy by sensitizing vulnerable neurons to caspase 3-mediated endoproteolysis of tau in a mouse model of Multiple Etiology Dementia.bioRxiv : the preprint server for biology · 2024Article
- Transcriptomic evaluation of tau and TDP-43 synergism shows tauopathy predominance and reveals potential modulating targets.Neurobiology of disease · 2024Article
- Transgenic Dendra2::tau expression allows in vivo monitoring of tau proteostasis in Caenorhabditis elegans.Disease models & mechanisms · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Although amyloid β (Aβ) and tau aggregates define the neuropathology of Alzheimer's disease (AD), TDP-43 has recently emerged as a co-morbid pathology in more than half of patients with AD. Individuals with concomitant Aβ, tau and TDP-43 pathology experience accelerated cognitive decline and worsened brain atrophy, but the molecular mechanisms of TDP-43 neurotoxicity in AD are unknown. Synergistic interactions among Aβ, tau and TDP-43 may be responsible for worsened disease outcomes. To study the biology underlying this process, we have developed new models of protein co-morbidity using the simple animal Caenorhabditis elegans. We demonstrate that TDP-43 specifically enhances tau but not Aβ neurotoxicity, resulting in neuronal dysfunction, pathological tau accumulation and selective neurodegeneration. Furthermore, we find that synergism between tau and TDP-43 is rescued by loss-of-function of the robust tau modifier sut-2. Our results implicate enhanced tau neurotoxicity as the primary driver underlying worsened clinical and neuropathological phenotypes in AD with TDP-43 pathology, and identify cell-type specific sensitivities to co-morbid tau and TDP-43. Determining the relationship between co-morbid TDP-43 and tau is crucial to understand, and ultimately treat, mixed pathology AD.
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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 OpenQuestion graph.