ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Tau seeds from Alzheimer's disease brains trigger tau spread in macaques while oligomeric-Aβ mediates pathology maturation.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- The biological scaling of Alzheimer's disease neuropathological changes across primate species.Alzheimer's research & therapy · 2025Pooled it
- Transaldolase 1 contributes to pentose phosphate pathway disruption and synaptic dysfunction in Alzheimer's disease.Translational neurodegeneration · 2026Article
- γ-radiation reduces phosphorylated-tau in rhesus macaque brains: potential implications for Alzheimer's disease and other tauopathies.Alzheimer's research & therapy · 2026Article
- γ-Radiation Reduces phosphorylated-Tau in RhesusMacaque Brains: Potential Implications forAlzheimer's Disease and other Tauopathies.Research square · 2026Article
- Tau PET overlap index correlation with neuropathological findings.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Targeting tau in Alzheimer's Disease: rationale, approach and challenges.Molecular neurodegeneration · 2026Review
- From seeds to symptoms: the molecular landscape of tau seeding in Alzheimer's disease.Frontiers in neuroscience · 2026Review
- Alzheimer's Tau seeds-induced pathology enhances hippocampal extracellular diffusion.Communications biology · 2025Article
- Integrating neuroinflammation biomarkers into the ATN(X) framework: Advances in Alzheimer's pathogenesis, diagnosis, and insights from non-human primate models.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Rational Modulation of Liquid-Liquid Phase Separation Offers Novel Ways to Combat Tauopathies.International journal of molecular sciences · 2025Review
- Additive effect of distant Lewy bodies and tau seeds injections on nigral degeneration in macaques.NPJ Parkinson's disease · 2025Article
- Seeding-competent early tau multimers are associated with cell type-specific transcriptional signatures.Acta neuropathologica · 2025Article
- Beyond Amyloid and Tau: The Critical Role of Microglia in Alzheimer's Disease Therapeutics.Biomedicines · 2025Review
- Tau and tauopathies across primate species: implications for modeling neurodegenerative disorders.Frontiers in aging neuroscience · 2025Review
- Temporal progression of tau pathology and neuroinflammation in a rhesus monkey model of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The Enigma of Tau Protein Aggregation: Mechanistic Insights and Future Challenges.International journal of molecular sciences · 2024Review
- Tau seeds from Alzheimer's disease brains trigger tau spread in macaques while oligomeric-Aβ mediates pathology maturation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The Role of Tau Pathology in Alzheimer's Disease and Down Syndrome.Journal of clinical medicine · 2024Review
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Authors and funding
18 authors at 7 institutions in 3 countries.
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Abstract
introductionThe "prion-like" features of Alzheimer's disease (AD) tauopathy and its relationship with amyloid-β (Aβ) have never been experimentally studied in primates phylogenetically close to humans.
methodsWe injected 17 macaques in the entorhinal cortex with nanograms of seeding-competent tau aggregates purified from AD brains or control extracts from aged-matched healthy brains, with or without intracerebroventricular co-injections of oligomeric-Aβ.
resultsPathological tau injection increased cerebrospinal fluid (CSF) p-tau181 concentration after 18 months. Tau pathology spreads from the entorhinal cortex to the hippocampal trisynaptic loop and the cingulate cortex, resuming the experimental progression of Braak stage I to IV. Many AD-related molecular networks were impacted by tau seeds injections regardless of Aβ injections in proteomic analyses. However, we found mature neurofibrillary tangles, increased CSF total-tau concentration, and pre- and postsynaptic degeneration only in Aβ co-injected macaques. DISCUSSION: Oligomeric-Aβ mediates the maturation of tau pathology and its neuronal toxicity in macaques but not its initial spreading. HIGHLIGHTS: This study supports the "prion-like" properties of misfolded tau extracted from AD brains. This study empirically validates the Braak staging in an anthropomorphic brain. This study highlights the role of oligomeric Aβ in driving the maturation and toxicity of tau pathology. This work establishes a novel animal model of early sporadic AD that is closer to the human pathology.
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