ArticlePLoS computational biology2021
Emergence of directional bias in tau deposition from axonal transport dynamics.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Hierarchical organization of tau topography across the Alzheimer's disease continuum integrates amyloid, connectome, and intrinsic molecular vulnerability.Communications biology · 2026Article
- Selective vulnerability and resilience to Alzheimer's disease tauopathy as a function of genes and the connectome.Brain : a journal of neurology · 2025Article
- Back to the Future: Predicting Individual Tau Progression in Alzheimer's Disease.Research square · 2025Article
- Directionality bias underpins divergent spatiotemporal progression of Alzheimer-related tauopathy in mouse models.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Extracellular PHF-tau modulates astrocyte mitochondrial dynamics and mediates neuronal connectivity.Translational neurodegeneration · 2025Article
- A network-level transport model of tau progression in the Alzheimer's brain.Mathematical medicine and biology : a journal of the IMA · 2025Article
- Cellular underpinnings of the selective vulnerability to tauopathic insults in Alzheimer's disease.bioRxiv : the preprint server for biology · 2023Article
- Connectome-based biophysics models of Alzheimer's disease diagnosis and prognosis.Translational research : the journal of laboratory and clinical medicine · 2023Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Defects in axonal transport may partly underpin the differences between the observed pathophysiology of Alzheimer's disease (AD) and that of other non-amyloidogenic tauopathies. Particularly, pathological tau variants may have molecular properties that dysregulate motor proteins responsible for the anterograde-directed transport of tau in a disease-specific fashion. Here we develop the first computational model of tau-modified axonal transport that produces directional biases in the spread of tau pathology. We simulated the spatiotemporal profiles of soluble and insoluble tau species in a multicompartment, two-neuron system using biologically plausible parameters and time scales. Changes in the balance of tau transport feedback parameters can elicit anterograde and retrograde biases in the distributions of soluble and insoluble tau between compartments in the system. Aggregation and fragmentation parameters can also perturb this balance, suggesting a complex interplay between these distinct molecular processes. Critically, we show that the model faithfully recreates the characteristic network spread biases in both AD-like and non-AD-like mouse tauopathy models. Tau transport feedback may therefore help link microscopic differences in tau conformational states and the resulting variety in clinical presentations.
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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 Socratic graph.