ArticleNeuropathology and applied neurobiology2022
Combinatorial model of amyloid β and tau reveals synergy between amyloid deposits and tangle formation.
Article in Neuropathology and applied neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 28 citations in OpenAlex.
- A murine model of amyloid enhanced tauopathy: progressive changes in tau pathology and behavior.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A murine model of amyloid-enhanced tauopathy: Comparison of wild-type and P301L-tau.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Attenuation of Tau-Mediated β-Amyloid1-42 Aggregation by Native PLGA Nanoparticles and Its Relevance to Alzheimer Disease Pathology.International journal of molecular sciences · 2026Article
- Fast Interneuron Dysfunction in Laminar Neural Mass Model Reproduces Alzheimer's Oscillatory Biomarkers.Human brain mapping · 2026Article
- The Biomarker Profile of Alzheimer's Disease for Disease-Modifying Treatment Eligibility: Questions and Debates.International journal of molecular sciences · 2025Review
- Acute targeting of N-terminal tau protein has long-lasting beneficial effects in Tg2576 APP/Aβ mouse model by reducing cognitive impairment, cerebral Aβ-amyloidosis, synaptic remodeling and microgliosis later in life.Acta neuropathologica communications · 2025Article
- Dual modulation of amyloid beta and tau aggregation and dissociation in Alzheimer's disease: a comprehensive review of the characteristics and therapeutic strategies.Translational neurodegeneration · 2025Review
- Native PLGA nanoparticles attenuate Aβ-seed induced tau aggregation under in vitro conditions: potential implication in Alzheimer's disease pathology.Scientific reports · 2024Article
- Seeing beyond the symptoms: biomarkers and brain regions linked to cognitive decline in Alzheimer's disease.Frontiers in aging neuroscience · 2024Article
- Humanized APOE genotypes influence lifespan independently of tau aggregation in the P301S mouse model of tauopathy.Acta neuropathologica communications · 2023Article
- Lipoprotein Metabolism, Protein Aggregation, and Alzheimer's Disease: A Literature Review.International journal of molecular sciences · 2023Review
- Soluble brain homogenates from diverse human and mouse sources preferentially seed diffuse Aβ plaque pathology when injected into newborn mouse hosts.Free neuropathology · 2022Article
- Induction of tauopathy in a mouse model of amyloidosis using intravenous administration of adeno-associated virus vectors expressing human P301L tau.Alzheimer's & dementia (New York, N. Y.)Article
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13 authors at 2 institutions in 1 country.
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Abstract
aimsTo illuminate the pathological synergy between Aβ and tau leading to emergence of neurofibrillary tangles (NFT) in Alzheimer's disease (AD), here, we have performed a comparative neuropathological study utilising three distinctive variants of human tau (WT tau, P301L mutant tau and S320F mutant tau). Previously, in non-transgenic mice, we showed that WT tau or P301L tau does not form NFT while S320F tau can spontaneously aggregate into NFT, allowing us to test the selective vulnerability of these different tau conformations to the presence of Aβ plaques.
methodsWe injected recombinant AAV-tau constructs into neonatal APP transgenic TgCRND8 mice or into 3-month-old TgCRND8 mice; both cohorts were aged 3 months post injection. This allowed us to test how different tau variants synergise with soluble forms of Aβ (pre-deposit cohort) or with frank Aβ deposits (post-deposit cohort).
resultsExpression of WT tau did not produce NFT or altered Aβ in either cohort. In the pre-deposit cohort, S320F tau induced Aβ plaque deposition, neuroinflammation and synaptic abnormalities, suggesting that early tau tangles affect the amyloid cascade. In the post-deposit cohort, contemporaneous expression of S320F tau did not exacerbate amyloid pathology, showing a dichotomy in Aβ-tau synergy based on the nature of Aβ. P301L tau produced NFT-type inclusions in the post-deposit cohort, but not in the pre-deposit cohort, indicating pathological synergy with pre-existing Aβ deposits.
conclusionsOur data show that different tau mutations representing specific folding variants of tau synergise with Aβ to different extents, depending on the presence of cerebral deposits.
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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.