ArticleScience advances2021
In vivo rate-determining steps of tau seed accumulation in Alzheimer's disease.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
69 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- The biological scaling of Alzheimer's disease neuropathological changes across primate species.Alzheimer's research & therapy · 2025Pooled it
- Shaping the future of preclinical development of successful disease-modifying drugs against Alzheimer's disease: a systematic review of tau propagation models.Acta neuropathologica communications · 2024Pooled it
- Site-specific phosphorylation of Ser352 drives aggregation of Tau R4 under acidosis conditions.Chemical science · 2026Article
- Tau Aggregate Imaging and Transcriptomics of Alzheimer's Disease Brain at Different Stages of Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Parent-of-origin effects in Alzheimer's liability dissociate neurocognitive and cardiovascular traits in at-risk individuals.Cell reports. Medicine · 2026Article
- Loss of endogenous tau suppresses APOE4-induced patterned behavioral decline and axon dysmorphia in a model of Alzheimer's disease.Disease models & mechanisms · 2026Article
- Elimination of tau tangles and soluble aggregates with the small molecule ACI-16664 prevents neurodegeneration in vivo.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Spatiotemporal dynamics of tau extent and load increase in Alzheimer's disease across four longitudinal cohorts.Nature aging · 2026Article
- Tau positron emission tomography analysis methods for the quantification of tau spread in preclinical and early Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Brain network dynamics determine tau presence while regional vulnerability governs tau load in Alzheimer's disease.Research square · 2026Article
- Dietary Bioactives in Alzheimer's Disease: A Critical Appraisal of Clinical Trials and Future Nutritional Strategies.Nutrients · 2026Review
- Decoupling phase separation and fibrillization preserves activity of biomolecular condensates.Nature communications · 2026Article
- DynamicalbioRxiv : the preprint server for biology · 2026Article
- A Mathematical Model of Cellular Aggregation Predicts Patterns of Tau Accumulation in Neurodegenerative Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Posterior Atrophy is a Neuroimaging Marker of Mild Cognitive Impairment in Parkinson's Disease.Noro psikiyatri arsivi · 2026Article
- Beyond prion-like spreading in neurodegenerative disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Hemispheric asymmetry of tau pathology is related to asymmetric amyloid deposition in Alzheimer's Disease.Nature communications · 2025Article
- Complex non-Markovian dynamics and the dual role of astrocytes in Alzheimer's disease development and propagation.Quantitative biology (Beijing, China) · 2025Article
- Tau profiling across Alzheimer's disease staging reveals vulnerability to disease pathophysiology.European journal of nuclear medicine and molecular imaging · 2025Article
- Evidence for trans-synaptic propagation of oligomeric tau in human progressive supranuclear palsy.Nature neuroscience · 2025Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
Both the replication of protein aggregates and their spreading throughout the brain are implicated in the progression of Alzheimer’s disease (AD). However, the rates of these processes are unknown and the identity of the rate-determining process in humans has therefore remained elusive. By bringing together chemical kinetics with measurements of tau seeds and aggregates across brain regions, we can quantify their replication rate in human brains. Notably, we obtain comparable rates in several different datasets, with five different methods of tau quantification, from postmortem seed amplification assays to tau PET studies in living individuals. Our results suggest that from Braak stage III onward, local replication, rather than spreading between brain regions, is the main process controlling the overall rate of accumulation of tau in neocortical regions. The number of seeds doubles only every ∼5 years. Thus, limiting local replication likely constitutes the most promising strategy to control tau accumulation during AD.
Identifiers
What OpenQuestion holds
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.