ArticleHuman molecular genetics2019
Tau/MAPT disease-associated variant A152T alters tau function and toxicity via impaired retrograde axonal transport.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Tau A152T risk variant drives distinct cell type transcriptional signatures in AD and PSP.Acta neuropathologica · 2026Article
- Amyloid exacerbates tau and alpha-synuclein pathologies, behavioral impairments, and neuroinflammation in a mixed dementia model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Deciphering cell type-specific causal genetic effects on brain imaging-derived phenotypes and disorders with single-cell Mendelian randomization.PLoS computational biology · 2026Article
- Article
- Evaluating MAPT p.A152T as a risk factor for the 3R tauopathy Pick's disease.Brain communications · 2026Article
- Heavy metal-induced disruption of the autophagy-lysosomal pathway: implications for aging and neurodegenerative disorders.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Review
- Mitochondrial Quality Control in Alzheimer's Disease: Insights fromAntioxidants (Basel, Switzerland) · 2024Review
- Reevaluating tau reduction as a therapeutic approach for tauopathies: Insights and perspectives.Cytoskeleton (Hoboken, N.J.) · 2024Article
- 17q21.31 Microduplication Syndrome in a Patient with Autism Spectrum Disorder, Macrocephaly, and Intellectual Disability.Reports (MDPI) · 2023Article
- Article
- Tauopathies: new perspectives and challenges.Molecular neurodegeneration · 2022Review
- Article
- Modelling the functional genomics of Parkinson's disease in Caenorhabditis elegans: LRRK2 and beyond.Bioscience reports · 2021Review
- High-content image-based analysis and proteomic profiling identifies Tau phosphorylation inhibitors in a human iPSC-derived glutamatergic neuronal model of tauopathy.Scientific reports · 2021Article
- Flavones 7,8-DHF, Quercetin, and Apigenin Against Tau ToxicityFrontiers in aging neuroscience · 2021Article
- The Crosstalk Between Pathological Tau Phosphorylation and Mitochondrial Dysfunction as a Key to Understanding and Treating Alzheimer's Disease.Molecular neurobiology · 2020Review
- Review
- Tauopathy-associated tau modifications selectively impact neurodegeneration and mitophagy in a novel C. elegans single-copy transgenic model.Molecular neurodegeneration · 2020Article
- Modeling tau transport in the axon initial segment.Mathematical biosciences · 2020Article
- Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation.Frontiers in neurology · 2020Review
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 3 countries.
Funding
Abstract
Mutations in the microtubule-associated protein tau (MAPT) underlie multiple neurodegenerative disorders, yet the pathophysiological mechanisms are unclear. A novel variant in MAPT resulting in an alanine to threonine substitution at position 152 (A152T tau) has recently been described as a significant risk factor for both frontotemporal lobar degeneration and Alzheimer's disease. Here we use complementary computational, biochemical, molecular, genetic and imaging approaches in Caenorhabditis elegans and mouse models to interrogate the effects of the A152T variant on tau function. In silico analysis suggests that a threonine at position 152 of tau confers a new phosphorylation site. This finding is borne out by mass spectrometric survey of A152T tau phosphorylation in C. elegans and mouse. Optical pulse-chase experiments of Dendra2-tau demonstrate that A152T tau and phosphomimetic A152E tau exhibit increased diffusion kinetics and the ability to traverse across the axon initial segment more efficiently than wild-type (WT) tau. A C. elegans model of tauopathy reveals that A152T and A152E tau confer patterns of developmental toxicity distinct from WT tau, likely due to differential effects on retrograde axonal transport. These data support a role for phosphorylation of the variant threonine in A152T tau toxicity and suggest a mechanism involving impaired retrograde axonal transport contributing to human neurodegenerative disease.
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Registered trials
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.