ArticleNeurobiology of disease2017
TDP-43 expression influences amyloidβ plaque deposition and tau aggregation.
Article in Neurobiology of disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 101 citations in OpenAlex.
- Brain morphometry patterns in the presence of Alzheimer's disease and/or LATE neuropathologic changes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- TDP-43 dysfunction facilitates the pathological conversion of tau.Molecular neurodegeneration · 2026Article
- Co-pathologies and biological processes beyond amyloid-beta and tau in people with Alzheimer's disease: Evidence from clinical cohort studies.Journal of internal medicine · 2026Review
- Molecular signatures and biomarker development for limbic-predominant age-related TDP-43 encephalopathy (LATE).Acta neuropathologica · 2026Review
- Calcineurin depletion coincides with phosphorylated TDP-43 deposition in a mouse model of ALS/FTLD-TDP.Acta neuropathologica communications · 2026Article
- Icaritin ameliorates mitochondrial dysfunction and autophagy impairment in cellular models of Alzheimer's disease.Frontiers in aging neuroscience · 2026Article
- Targeting protein aggregate co-pathologies in neurodegeneration: a viable therapeutic strategy?Molecular neurodegeneration advances · 2026Review
- Direct interaction between TDP-43 and Tau promotes their co-condensation, while suppressing Tau fibril formation and seeding.The EMBO journal · 2025Article
- Differences and overlaps in TDP-43 pathology of 'pure' LATE-NC compared to LATE-NC coexisting with Alzheimer's disease.Acta neuropathologica · 2025Article
- A cellular model of TDP-43 induces phosphorylated TDP-43 aggregation with distinct changes in solubility and autophagy dysregulation.The FEBS 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
- Pathogenic oligomeric Tau alters neuronal RNA processes through the formation of nuclear heteromeric amyloids with RNA-binding protein Musashi1.Progress in neurobiology · 2025Article
- Cytoplasmic expression of trans-active response DNA-binding protein-43 in aged mice display hippocampal sclerosis-like degeneration and neuronal loss with reduced lifespan.Journal of neuropathology and experimental neurology · 2025Article
- TDP43 is a newly identified substrate for PS1, enhancing the expression of APP following cleavage.Cell death discovery · 2025Article
- 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
- 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
- Senile plaque-associated transactive response DNA-binding protein 43 in Alzheimer's disease: A case report spanning 16 years of memory loss.Neuropathology : official journal of the Japanese Society of Neuropathology · 2024Article
- Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer's disease mice.Journal of translational medicine · 2024Article
- Long-term normalization of calcineurin activity in model mice rescues Pin1 and attenuates Alzheimer's phenotypes without blocking peripheral T cell IL-2 response.Alzheimer's research & therapy · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Although the main focus in Alzheimer's disease (AD) has been an investigation of mechanisms causing Aβ plaque deposition and tau tangle formation, recent studies have shown that phosphorylated TDP-43 pathology is present in up to 50% of sporadic cases. Furthermore, elevated phosphorylated TDP-43 has been associated with more severe AD pathology. Therefore, we hypothesized that TDP-43 may regulate amyloid-beta precursor protein (APP) trafficking and tau phosphorylation/aggregation. In order to examine the role of TDP-43 in AD, we developed a transgenic mouse that overexpresses hippocampal and cortical neuronal TDP-43 in a mouse expressing familial mutations (K595N and M596L) in APP and presenilin 1 (PSEN1ΔE9). In our model, increased TDP-43 was related to increased tau aggregation as evidenced by thioflavin S-positive phosphorylated tau, which may implicate TDP-43 expression in pre-tangle formation. In addition, there was increased endosomal/lysosomal localization of APP and reduced Aβ plaque formation with increased TDP-43. Furthermore, there was decreased calcineurin with elevated TDP-43 expression. Since calcineurin is a phosphatase for TDP-43, the decreased calcineurin expression may be one mechanism leading to an increase in accumulation of diffuse phosphorylated TDP-43 in the hippocampus and cortex. We further show that when TDP-43 is knocked down there is an increase in calcineurin. In our model of selective TDP-43 overexpression in an APP/PSEN1 background, we show that TDP-43 decreases Aβ plaque deposition while increasing abnormal tau aggregation. These observations indicate that TDP-43 may play a role in regulating APP trafficking and tau aggregation. Our data suggest that TDP-43 could be a putative target for therapeutic intervention in AD affecting both Aβ plaque formation and tauopathy.
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