ArticleActa neuropathologica2023
Tau seeding and spreading in vivo is supported by both AD-derived fibrillar and oligomeric tau.
Article in Acta neuropathologica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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37 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- 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
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Mitochondrial NADK2-dependent NADPH controls tau oligomer uptake in human neurons.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Extracellular Vesicles in Alzheimer's Disease: Mechanisms, Biomarkers, and Therapeutic Engineering.International journal of molecular sciences · 2026Review
- Extracellular Protein Quality Control in Tau Pathology.Molecular neurobiology · 2026Review
- Tau in Alzheimer's disease: Shaping the future patient journey.The journal of prevention of Alzheimer's disease · 2026Review
- Early synaptic pathology is associated with small tau aggregates in Alzheimer's disease.Acta neuropathologica · 2026Article
- Research Progress on the Pathogenesis, Therapeutic Strategies, and Phthalocyanine Compounds for Alzheimer's Disease.Current Alzheimer research · 2026Review
- Seed-competent tau oligomers' activity correlates with the rate of progression in sporadic Alzheimer's disease patients.Journal of Alzheimer's disease : JAD · 2026Article
- 4R-tau seeding activity reveals molecular subtypes in progressive supranuclear palsy.Nature communications · 2025Article
- Molecular polymorphism of tau aggregates in Pick's disease.Neurobiology of disease · 2025Article
- Seeding Alzheimer's disease-associated tau pathology in MAPT knock-in primary neurons causes early axonopathy and synaptic dysfunction.Scientific reports · 2025Article
- Neuronal gene profiling of tau oligomer-bearing cholinergic nucleus basalis neurons during the onset of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- A brain-derived tau oligomer polymorph is associated with cognitive resilience to Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Article
- Soluble and Insoluble Lysates from the Human A53T Mutant α-Synuclein Transgenic Mouse Model Induces α-Synucleinopathy Independent of Injection Site.International journal of molecular sciences · 2025Article
- Tau-seed interactome analysis reveals distinct functional signatures in Alzheimer's disease across model systems.bioRxiv : the preprint server for biology · 2025Article
- hiPSC-neurons recapitulate the subtype-specific cell intrinsic nature of susceptibility to neurodegenerative disease-relevant aggregation.Acta neuropathologica communications · 2025Article
- Multimodal spatial gradients to explain regional susceptibility to fibrillar tau in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Tau, synapse loss and gliosis progress in an Alzheimer's mouse model after amyloid-β immunotherapy.Brain : a journal of neurology · 2025Article
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Abstract
Insoluble fibrillar tau, the primary constituent of neurofibrillary tangles, has traditionally been thought to be the biologically active, toxic form of tau mediating neurodegeneration in Alzheimer's disease. More recent studies have implicated soluble oligomeric tau species, referred to as high molecular weight (HMW), due to their properties on size-exclusion chromatography, in tau propagation across neural systems. These two forms of tau have never been directly compared. We prepared sarkosyl-insoluble and HMW tau from the frontal cortex of Alzheimer patients and compared their properties using a variety of biophysical and bioactivity assays. Sarkosyl-insoluble fibrillar tau comprises abundant paired-helical filaments (PHF) as quantified by electron microscopy (EM) and is more resistant to proteinase K, compared to HMW tau, which is mostly in an oligomeric form. Sarkosyl-insoluble and HMW tau are nearly equivalent in potency in HEK cell bioactivity assay for seeding aggregates, and their injection reveals similar local uptake into hippocampal neurons in PS19 Tau transgenic mice. However, the HMW preparation appears to be far more potent in inducing a glial response including Clec7a-positive rod microglia in the absence of neurodegeneration or synapse loss and promotes more rapid propagation of misfolded tau to distal, anatomically connected regions, such as entorhinal and perirhinal cortices. These data suggest that soluble HMW tau has similar properties to fibrillar sarkosyl-insoluble tau with regard to tau seeding potential, but may be equal or even more bioactive with respect to propagation across neural systems and activation of glial responses, both relevant to tau-related Alzheimer phenotypes.
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