ArticleActa neuropathologica communications2021
Ultrasensitive tau biosensor cells detect no seeding in Alzheimer's disease CSF.
Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 78 citations in OpenAlex.
- Endolysosomal inhibition uncouples tau uptake from intracellular seeding.The Journal of biological chemistry · 2026Article
- Reducing PI4KIIIα Levels or Activity Limits Tau Seed Internalization and Assembly in Human Cortical Neurons.Cells · 2026Article
- Cysteines are critical determinants of spontaneous and seeded tau aggregation in cells.Research square · 2026Article
- Predifferentiation Neurotoxicity of GenX Exposure on hiPSC-Derived Cortical Neurons.Environmental science & technology · 2026Article
- Cysteines are critical determinants of spontaneous and seeded tau aggregation in cells.bioRxiv : the preprint server for biology · 2026Article
- Preclinical Development of a Vectorized Artificial miRNA Gene Therapy for Tauopathies.bioRxiv : the preprint server for biology · 2025Article
- DnaJB1 chaperone inhibits tau aggregation by recognizing its N-terminus.bioRxiv : the preprint server for biology · 2025Article
- Article
- Tau seeding activity in the cerebrospinal fluid of Alzheimer disease patients predicts short-term cognitive decline.Alzheimer's research & therapy · 2025Article
- Water-directed pinning is key to tau prion formation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Functional classification of tauopathy strains reveals the role of protofilament core residues.Science advances · 2025Article
- VCP regulates early tau seed amplification via specific cofactors.Molecular neurodegeneration · 2025Article
- Optical biosensors for diagnosing neurodegenerative diseases.Npj biosensing · 2025Review
- A novel peptide-based tau aggregation inhibitor as a potential therapeutic for Alzheimer's disease and other tauopathies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Co-opting templated aggregation to degrade pathogenic tau assemblies and improve motor function.Cell · 2024Article
- In situ seeding assay: A novel technique for direct tissue localization of bioactive tau.Journal of neuropathology and experimental neurology · 2024Article
- Modeling late-onset Alzheimer's disease neuropathology via direct neuronal reprogramming.Science (New York, N.Y.) · 2024Article
- Developmental neurotoxicity of PFOA exposure on hiPSC-derived cortical neurons.Environment international · 2024Article
- DNAJB8 oligomerization is mediated by an aromatic-rich motif that is dispensable for substrate activity.Structure (London, England : 1993) · 2024Article
- VCP regulates early tau seed amplification via specific cofactors.Research square · 2024Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Tau protein forms self-replicating assemblies (seeds) that may underlie progression of pathology in Alzheimer's disease (AD) and related tauopathies. Seeding in recombinant protein preparations and brain homogenates has been quantified with "biosensor" cell lines that express tau with a disease-associated mutation (P301S) fused to complementary fluorescent proteins. Quantification of induced aggregation in cells that score positive by fluorescence resonance energy transfer (FRET) is accomplished by cell imaging or flow cytometry. Several groups have reported seeding activity in antemortem cerebrospinal fluid (CSF) using various methods, but these findings are not yet widely replicated. To address this question, we created two improved FRET-based biosensor cell lines based on tau expression, termed version 2 low (v2L) and version 2 high (v2H). We determined that v2H cells are ~ 100-fold more sensitive to AD-derived tau seeds than our original lines, and coupled with immunoprecipitation reliably detect seeding from samples containing as little as 100 attomoles of recombinant tau fibrils or ~ 32 pg of total protein from AD brain homogenate. We tested antemortem CSF from 11 subjects with a clinical diagnosis of AD, 9 confirmed by validated CSF biomarkers. We used immunoprecipitation coupled with seed detection in v2H cells and detected no tau seeding in any sample. Thus we cannot confirm prior reports of tau seeding activity in the CSF of AD patients. This next generation of ultra-sensitive tau biosensors may nonetheless be useful to the research community to quantify tau pathology as sensitively and specifically as possible.
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