ArticleJournal of visualized experiments : JoVE2015
Sensitive Detection of Proteopathic Seeding Activity with FRET Flow Cytometry.
Article in Journal of visualized experiments : JoVE, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 100 citations in OpenAlex.
- Protocol for efficient purification of endotoxin-free human recombinant tau protein.STAR protocols · 2026Article
- Nuclear dysfunction in aging and neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- High-throughput screening approach identifies substrate-selective Hsp104 variants that counter amyloid seeding with diminished off-target effects.Molecular cell · 2026Article
- Molecular profiling of alpha-synuclein pathology and seeding activity in Parkinson's disease.Acta neuropathologica · 2026Article
- Integrative genomic and functional analyses reveal NINL as a modulator of tau aggregation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- The Hsp40 cochaperone DNAJC7 regulates polyglutamine aggregation and exhibits context-dependent effects on polyglycine aggregation.The Journal of biological chemistry · 2026Article
- A quantitative cell-based reporter links TDP-43 aggregation and dysfunction to define pathogenic mechanisms.PLoS biology · 2026Article
- Early onset rapidly progressive frontotemporal dementia due to a novel MAPT P301A variant with functional validation of pathogenicity.NPJ dementia · 2026Article
- Integrative Genomic and Functional Analyses Reveal NINL as a Modulator of Tau Aggregation.bioRxiv : the preprint server for biology · 2025Article
- Article
- 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
- Differential effects of age and sex on tau pathology propagation in the htau mouse model: A neuropathological and proteomic study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- β-Amyloid induces microglial expression of GPC4 and APOE leading to increased neuronal tau pathology and toxicity.Molecular neurodegeneration · 2025Article
- Article
- 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
- Human MAPT knockin mouse models of frontotemporal dementia for the neurodegenerative research community.Cell reports methods · 2025Article
- In vivo hyperphosphorylation of tau is associated with synaptic loss and behavioral abnormalities in the absence of tau seeds.Nature neuroscience · 2025Article
- The role of microglia in the prion-like transmission of protein aggregates in neurodegeneration.Brain communications · 2025Review
- DNAJB8 oligomerization is mediated by an aromatic-rich motif that is dispensable for substrate activity.Structure (London, England : 1993) · 2024Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Increasing evidence supports transcellular propagation of toxic protein aggregates, or proteopathic seeds, as a mechanism for the initiation and progression of pathology in several neurodegenerative diseases, including Alzheimer's disease and the related tauopathies. The potentially critical role of tau seeds in disease progression strongly supports the need for a sensitive assay that readily detects seeding activity in biological samples. By combining the specificity of fluorescence resonance energy transfer (FRET), the sensitivity of flow cytometry, and the stability of a monoclonal cell line, an ultra-sensitive seeding assay has been engineered and is compatible with seed detection from recombinant or biological samples, including human and mouse brain homogenates. The assay employs monoclonal HEK 293T cells that stably express the aggregation-prone repeat domain (RD) of tau harboring the disease-associated P301S mutation fused to either CFP or YFP, which produce a FRET signal upon protein aggregation. The uptake of proteopathic tau seeds (but not other proteins) into the biosensor cells stimulates aggregation of RD-CFP and RD-YFP, and flow cytometry sensitively and quantitatively monitors this aggregation-induced FRET. The assay detects femtomolar concentrations (monomer equivalent) of recombinant tau seeds, has a dynamic range spanning three orders of magnitude, and is compatible with brain homogenates from tauopathy transgenic mice and human tauopathy subjects. With slight modifications, the assay can also detect seeding activity of other proteopathic seeds, such as α-synuclein, and is also compatible with primary neuronal cultures. The ease, sensitivity, and broad applicability of FRET flow cytometry makes it useful to study a wide range of protein aggregation disorders.
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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.