Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 45

The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.

RNA induces unique tau strains and stabilizes Alzheimer’s disease seeds

Zwierzchowski-Zarate, Amy N., Mendoza-Oliva, Aydé, Kashmer, Omar M., Collazo-Lopez, Josue E., White, Charles L., Diamond, Marc I.·2022·Journal of Biological Chemistry
DOI 10.1016/j.jbc.2022.102132PMC PMC9364032

Published version of a preprint

Open this paper in CoChat — free account

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.jbc.2022.102132

Cites

21 of 21 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Tau nonselectively binds RNA yet seeding and fibrilization are specific.A, BLI with tau immobilized onto AR2G biosensors and exposed to increasing concentrations of PolyA, or C RNA (half-log dilutions: 0.13 μM (red), 0.4 μM (dark blue), 1.3 μM (green), 4 μM (light blue), 13 μM (orange), and 41 μM (black)). Tau bound all RNA with similar avidity, association, and dissociation rates. Figure shows representative data of polyA or polyC RNA binding to BLI AR2G sensors loaded with tau. KDAPP calculated as mean of three independent experiments. Binding (nm) refers to the wavelength perturbation in reflected light from the biosensor. Red lines represent curves fit to primary data. See Table 1 and Fig. S1 for more data on these experiments. B, tau monomer incubated 24 h with nucleic acid before transduction of v2L biosensors. Intracellular aggregation was quantified as % FRET positive via flow cytometry. Specific nucleic acids induced seed-competency in tau (human total RNA p < 0.0001, polyA RNA p < 0.0001, ssDNA Seq1 p = 0.0007, ssDNA Seq1′ p = 0.0002) while others did not (polyU RNA p = 0.98, polyC RNA p = 0.99, dsRNA p = 0.99, dsDNA p = 0.99, RNA/DNA p = 0.98). p values calculated with one-way ANOVA, post-hoc Dunnett’s multiple comparisons test. C, after 1 week with indicated inducer, tau was deposited on 400CF grids (4 μM) and stained with 2% uranyl acetate. Grids were scanned with TEM for fibrils, and representative images are shown. No fibrils were seen for no inducer, polyU, or polyC. Fibrils were observed only in conditions that induced seeding (polyA). Scale bar = 500 nm. D, tau monomer incubated with various molar ratios of polyA for 24 h before induction of biosensors. 2:1 Tau to RNA (8 μM:4 μM) ratio produced optimal seeding. E and F, seeding of tau following incubation with various lengths (nt) of polyA RNA for 2 (E) or 7 (F) days before transducing biosensors. >40 nt was required for tau seeding. (2 days versus 0, p = 0.97 10mer, p > 0.99 20mer, p = 0.99 30mer, p < 0.0001 40mer; 7 days versus 0, p = 0.99 10mer, p > 0.99 20mer, p = 0.15 30mer, p < 0.0001 40mer) p values calculated with one-way ANOVA, post-hoc Dunnett’s multiple comparisons test. All seeding data represents two experimental replicates, each performed in technical triplicate. These experiments are representative of similar studies performed 19 times overall for (B), and five times overall for (D-F). Error bars = S.D. ∗∗∗∗p < 0.0001, ∗∗∗p < 0.001.
Figure 1 Tau nonselectively binds RNA yet seeding and fibrilization are specific.A, BLI with tau immobilized onto AR2G biosensors and exposed to increasing concentrations of PolyA, or C RNA (half-log dilutions: 0.13 μM (red), 0.4 μM (dark blue), 1.3 μM (green), 4 μM (light blue), 13 μM (orange), and 41 μM (black)). Tau bound all RNA with similar avidity, association, and dissociation rates. Figure shows representative data of polyA or polyC RNA binding to BLI AR2G sensors loaded with tau. KDAPP calculated as mean of three independent experiments. Binding (nm) refers to the wavelength perturbation in reflected light from the biosensor. Red lines represent curves fit to primary data. See Table 1 and Fig. S1 for more data on these experiments. B, tau monomer incubated 24 h with nucleic acid before transduction of v2L biosensors. Intracellular aggregation was quantified as % FRET positive via flow cytometry. Specific nucleic acids induced seed-competency in tau (human total RNA p < 0.0001, polyA RNA p < 0.0001, ssDNA Seq1 p = 0.0007, ssDNA Seq1′ p = 0.0002) while others did not (polyU RNA p = 0.98, polyC RNA p = 0.99, dsRNA p = 0.99, dsDNA p = 0.99, RNA/DNA p = 0.98). p values calculated with one-way ANOVA, post-hoc Dunnett’s multiple comparisons test. C, after 1 week with indicated inducer, tau was deposited on 400CF grids (4 μM) and stained with 2% uranyl acetate. Grids were scanned with TEM for fibrils, and representative images are shown. No fibrils were seen for no inducer, polyU, or polyC. Fibrils were observed only in conditions that induced seeding (polyA). Scale bar = 500 nm. D, tau monomer incubated with various molar ratios of polyA for 24 h before induction of biosensors. 2:1 Tau to RNA (8 μM:4 μM) ratio produced optimal seeding. E and F, seeding of tau following incubation with various lengths (nt) of polyA RNA for 2 (E) or 7 (F) days before transducing biosensors. >40 nt was required for tau seeding. (2 days versus 0, p = 0.97 10mer, p > 0.99 20mer, p = 0.99 30mer, p < 0.0001 40mer; 7 days versus 0, p = 0.99 10mer, p > 0.99 20mer, p = 0.15 30mer, p < 0.0001 40mer) p values calculated with one-way ANOVA, post-hoc Dunnett’s multiple comparisons test. All seeding data represents two experimental replicates, each performed in technical triplicate. These experiments are representative of similar studies performed 19 times overall for (B), and five times overall for (D-F). Error bars = S.D. ∗∗∗∗p < 0.0001, ∗∗∗p < 0.001.CC BY · PubMed Central
Figure 2 Stabilization of tau fibrils and seeds in vitro.A, tau fibrils preformed with polyA RNA or heparin were treated with RNase (T1 and A, 316 U/μl and 3.2 mg/ml), DNase (I, 633 U/μl), or heparinase I (3797 U/ml) for 24 h before transduction of biosensors. (+) signifies RNase treatment added to fibrils at same time as seeding, with no pre-incubation. Seeds formed with polyA were sensitive to RNase treatment (p < 0.0001). RNase added directly to seeds at the time of seeding had no effect (p = 0.49). DNase and heparinase treatment did not affect seeds formed by polyA (p = 0.99 and 0.97). Seeds formed with heparin were sensitive to heparinase treatment (p < 0.0001), but not RNase or DNase (p = 0.09 RNase, p > 0.99 immediate RNase, p = 0.24 DNase). p values were calculated with one-way repeated measures ANOVA, post-hoc Dunnett’s multiple comparisons test, comparing control to enzyme treated conditions for both polyA and heparin fibrils. Seeding data represents two experimental replicates, each performed in technical triplicate. These experiments are representative of similar studies performed 15 times overall. Error bars = S.D. B, TEM 400CF grids containing tau (4 μM) stained with 2% UA. All grids were scanned; representative images are shown. Scale bar = 200 nm. Fibrils formed by polyA lose integrity after exposure to RNase, but not heparinase. Heparin fibrils were undetectable after heparinase treatment, but not RNase. FRET, fluorescence resonance energy transfer. ∗∗∗∗p < 0.0001.
Figure 2 Stabilization of tau fibrils and seeds in vitro.A, tau fibrils preformed with polyA RNA or heparin were treated with RNase (T1 and A, 316 U/μl and 3.2 mg/ml), DNase (I, 633 U/μl), or heparinase I (3797 U/ml) for 24 h before transduction of biosensors. (+) signifies RNase treatment added to fibrils at same time as seeding, with no pre-incubation. Seeds formed with polyA were sensitive to RNase treatment (p < 0.0001). RNase added directly to seeds at the time of seeding had no effect (p = 0.49). DNase and heparinase treatment did not affect seeds formed by polyA (p = 0.99 and 0.97). Seeds formed with heparin were sensitive to heparinase treatment (p < 0.0001), but not RNase or DNase (p = 0.09 RNase, p > 0.99 immediate RNase, p = 0.24 DNase). p values were calculated with one-way repeated measures ANOVA, post-hoc Dunnett’s multiple comparisons test, comparing control to enzyme treated conditions for both polyA and heparin fibrils. Seeding data represents two experimental replicates, each performed in technical triplicate. These experiments are representative of similar studies performed 15 times overall. Error bars = S.D. B, TEM 400CF grids containing tau (4 μM) stained with 2% UA. All grids were scanned; representative images are shown. Scale bar = 200 nm. Fibrils formed by polyA lose integrity after exposure to RNase, but not heparinase. Heparin fibrils were undetectable after heparinase treatment, but not RNase. FRET, fluorescence resonance energy transfer. ∗∗∗∗p < 0.0001.CC BY · PubMed Central
Figure 3 RNA inducer dictates aggregate maintenance and strain identity.A, Tau seeds derived from different nucleic acid sources were transduced into DS1 cells, and single cells were sorted into 96-well plates and monitored over time. Certain nucleic acids (human, polyA) created more stable strains than others (ssDNA, yeast), which lost aggregates or sectored almost completely. N = 130 derived from human RNA, 228 from polyA, 220 from DNA, and 98 from yeast RNA. B, stable colonies containing inclusions were imaged using an In Cell Analyzer 6000, and resulting images were scored for morphology, blinded to the method of seed induction. Distribution of morphologies varied by inducer. N = 78 derived from human RNA, 99 from polyA, and 7 from ssDNA, 1 from yeast. C, exemplars of morphologies. Scale bar = 6 μm.
Figure 3 RNA inducer dictates aggregate maintenance and strain identity.A, Tau seeds derived from different nucleic acid sources were transduced into DS1 cells, and single cells were sorted into 96-well plates and monitored over time. Certain nucleic acids (human, polyA) created more stable strains than others (ssDNA, yeast), which lost aggregates or sectored almost completely. N = 130 derived from human RNA, 228 from polyA, 220 from DNA, and 98 from yeast RNA. B, stable colonies containing inclusions were imaged using an In Cell Analyzer 6000, and resulting images were scored for morphology, blinded to the method of seed induction. Distribution of morphologies varied by inducer. N = 78 derived from human RNA, 99 from polyA, and 7 from ssDNA, 1 from yeast. C, exemplars of morphologies. Scale bar = 6 μm.CC BY · PubMed Central
Figure 4 RNA stabilizes soluble seeds from AD brain. Homogenate from AD brain was fractionated in sarkosyl via ultracentrifugation. The supernatant (sup) was further fractionated using SEC. A, resultant fractions were treated with RNase, DNase, or vehicle for 24 h and seeded onto v2L biosensors. The percentage of FRET-positive cells was determined at 48 h. Soluble AD seeds (Sup, >10mer, ∼10mer, trimer, monomer) were highly sensitive to RNase (Sup, >10mer, ∼10mer p < 0.0001, trimer p = 0.0025, monomer p = 0.015, multiple unpaired t tests as compared to control) but not DNase (Sup p = 0.54, >10mer p = 0.68, ∼10mer p = 0.74, trimer p = 0.49, monomer p = 0.45, multiple unpaired t tests as compared to control). Sarkosyl insoluble (SI) AD fibrils were unchanged in all conditions (p = 0.65 RNase versus control, p = 0.28 DNase versus control). Graphs represent data from two experimental replicates, each performed in technical triplicate. These experiments are representative of similar studies performed 12 times overall. Error bars = S.D. B, data from A normalized to untreated control seeding (% FRET positive). AD, Alzheimer’s disease; FRET, fluorescence resonance energy transfer; SEC, size-exclusion chromatography. ∗∗∗∗p < 0.0001, ∗∗∗p < 0.001, ∗∗p < 0.01, ∗p < 0.05.
Figure 4 RNA stabilizes soluble seeds from AD brain. Homogenate from AD brain was fractionated in sarkosyl via ultracentrifugation. The supernatant (sup) was further fractionated using SEC. A, resultant fractions were treated with RNase, DNase, or vehicle for 24 h and seeded onto v2L biosensors. The percentage of FRET-positive cells was determined at 48 h. Soluble AD seeds (Sup, >10mer, ∼10mer, trimer, monomer) were highly sensitive to RNase (Sup, >10mer, ∼10mer p < 0.0001, trimer p = 0.0025, monomer p = 0.015, multiple unpaired t tests as compared to control) but not DNase (Sup p = 0.54, >10mer p = 0.68, ∼10mer p = 0.74, trimer p = 0.49, monomer p = 0.45, multiple unpaired t tests as compared to control). Sarkosyl insoluble (SI) AD fibrils were unchanged in all conditions (p = 0.65 RNase versus control, p = 0.28 DNase versus control). Graphs represent data from two experimental replicates, each performed in technical triplicate. These experiments are representative of similar studies performed 12 times overall. Error bars = S.D. B, data from A normalized to untreated control seeding (% FRET positive). AD, Alzheimer’s disease; FRET, fluorescence resonance energy transfer; SEC, size-exclusion chromatography. ∗∗∗∗p < 0.0001, ∗∗∗p < 0.001, ∗∗p < 0.01, ∗p < 0.05.CC BY · PubMed Central
Figure 5 Model of RNA:tau seeding and strain propagation.A, RNA serves as a sequence-specific inducer of tau seeds and strains. Stable cellular replication of a given strain depends on compatible RNA to be present as a co-factor. B, in the absence of compatible RNA, a given RNA-induced strain will replicate inefficiently.
Figure 5 Model of RNA:tau seeding and strain propagation.A, RNA serves as a sequence-specific inducer of tau seeds and strains. Stable cellular replication of a given strain depends on compatible RNA to be present as a co-factor. B, in the absence of compatible RNA, a given RNA-induced strain will replicate inefficiently.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 21 references

Research works printed but not linked: 50

  1. Lee, 2001, Neurodegenerative tauopathies, Annu. Rev. Neurosci., 24, 1121, 10.1146/annurev.neuro.24.1.1121 · DOI · Paper page
  2. Sanders, 2014, Distinct tau prion strains propagate in cells and mice and define different tauopathies, Neuron, 82, 1271, 10.1016/j.neuron.2014.04.047 · DOI · Paper page
  3. Calafate, 2015, Synaptic contacts enhance cell-to-cell tau pathology propagation, Cell Rep., 11, 1176, 10.1016/j.celrep.2015.04.043 · DOI
  4. Kaufman, 2016, Tau prion strains dictate patterns of cell pathology, progression rate, and regional vulnerability in vivo, Neuron, 92, 796, 10.1016/j.neuron.2016.09.055 · DOI · Paper page
  5. Clavaguera, 2013, Brain homogenates from human tauopathies induce tau inclusions in mouse brain, Proc. Natl. Acad. Sci. U. S. A., 110, 9535, 10.1073/pnas.1301175110 · DOI
  6. Sharma, 2018, Tau monomer encodes strains, Elife, 7, 10.7554/eLife.37813 · DOI · Paper page
  7. Mirbaha, 2022, Seed-competent tau monomer initiates pathology in PS19 tauopathy mice, bioRxiv
  8. Friedhoff, 1998, Rapid assembly of Alzheimer-like paired helical filaments from microtubule-associated protein tau monitored by fluorescence in solution, Biochemistry, 37, 10223, 10.1021/bi980537d · DOI · Paper page
  9. Pérez, 1996, Polymerization of tau into filaments in the presence of heparin: The minimal sequence required for tau-tau interaction, J. Neurochem., 67, 1183, 10.1046/j.1471-4159.1996.67031183.x · DOI
  10. Wilson, 1997, Free fatty acids stimulate the polymerization of tau and amyloid beta peptides. In vitro evidence for a common effector of pathogenesis in Alzheimer's disease, Am. J. Pathol., 150, 2181
  11. Chirita, 2003, Anionic micelles and vesicles induce tau fibrillization in vitro, J. Biol. Chem., 278, 25644, 10.1074/jbc.M301663200 · DOI
  12. Kampers, 1996, RNA stimulates aggregation of microtubule-associated protein tau into Alzheimer-like paired helical filaments, FEBS Lett., 399, 344, 10.1016/S0014-5793(96)01386-5 · DOI · Paper page
  13. Bryan, 1975, Inhibition of tubulin assembly by RNA and other polyanions: Evidence for a required protein, Proc. Natl. Acad. Sci. U. S. A., 72, 3570, 10.1073/pnas.72.9.3570 · DOI · Paper page
  14. Ginsberg, 1997, Sequestration of RNA in Alzheimer's disease neurofibrillary tangles and senile plaques, Ann. Neurol., 41, 200, 10.1002/ana.410410211 · DOI
  15. Ginsberg, 1998, RNA sequestration to pathological lesions of neurodegenerative diseases, Acta Neuropathol., 96, 487, 10.1007/s004010050923 · DOI
  16. Lester, 2021, Tau aggregates are RNA-protein assemblies that mislocalize multiple nuclear speckle components, Neuron, 109, 1675, 10.1016/j.neuron.2021.03.026 · DOI · Paper page
  17. Mukrasch, 2007, The "jaws" of the tau-microtubule interaction, J. Biol. Chem., 282, 12230, 10.1074/jbc.M607159200 · DOI
  18. Holmes, 2014, Proteopathic tau seeding predicts tauopathy in vivo, Proc. Natl. Acad. Sci. U. S. A., 111, E4376, 10.1073/pnas.1411649111 · DOI · Paper page
  19. Hartl, 2017, Protein misfolding diseases, Annu. Rev. Biochem., 86, 21, 10.1146/annurev-biochem-061516-044518 · DOI
  20. Mirbaha, 2018, Inert and seed-competent tau monomers suggest structural origins of aggregation, Elife, 7, 10.7554/eLife.36584 · DOI
  21. Hou, 2021, Biophysical properties of a tau seed, Sci. Rep., 11, 10.1038/s41598-021-93093-z · DOI
  22. Koren, 2020, Tau-mediated dysregulation of RNA: evidence for a common molecular mechanism of toxicity in frontotemporal dementia and other tauopathies, Neurobiol. Dis., 141, 10.1016/j.nbd.2020.104939 · DOI · Paper page
  23. Rybak-Wolf, 2021, RNA dynamics in Alzheimer's disease, Molecules, 26, 5113, 10.3390/molecules26175113 · DOI
  24. Gunawardana, 2015, The human tau interactome: binding to the ribonucleoproteome, and impaired binding of the proline-to-leucine mutant at position 301 (P301L) to chaperones and the proteasome, Mol. Cell Proteomics, 14, 3000, 10.1074/mcp.M115.050724 · DOI · Paper page
  25. Meier, 2015, Identification of novel tau interactions with endoplasmic reticulum proteins in Alzheimer's disease brain, J. Alzheimers Dis., 48, 687, 10.3233/JAD-150298 · DOI
  26. Banerjee, 2020, Tau protein- induced sequestration of the eukaryotic ribosome: implications in neurodegenerative disease, Sci. Rep., 10, 5225, 10.1038/s41598-020-61777-7 · DOI
  27. Jessus, 1984, In vitro inhibition of tubulin assembly by a ribonucleoprotein complex associated with the free ribosome fraction isolated from Xenopus laevis oocytes: effect at the level of microtubule-associated proteins, Cell Differ., 14, 179, 10.1016/0045-6039(84)90044-7 · DOI
  28. Evans, 2021, Altered ribosomal function and protein synthesis caused by tau, Acta Neuropathol. Commun., 9, 110, 10.1186/s40478-021-01208-4 · DOI
  29. Montalbano, 2021, Tau modulates mRNA transcription, Alternative polyadenylation profiles of hnRNPs, chromatin remodeling and spliceosome complexes, Front. Mol. Neurosci., 14, 742790, 10.3389/fnmol.2021.742790 · DOI
  30. Evans, 2019, Decreased synthesis of ribosomal proteins in tauopathy revealed by non-canonical amino acid labelling, EMBO J, 38, 10.15252/embj.2018101174 · DOI · Paper page
  31. Wolozin, 2012, Regulated protein aggregation: stress granules and neurodegeneration, Mol. Neurodegener, 7, 56, 10.1186/1750-1326-7-56 · DOI
  32. Vanderweyde, 2016, Interaction of tau with the RNA-binding protein TIA1 regulates tau pathophysiology and toxicity, Cell Rep., 15, 1455, 10.1016/j.celrep.2016.04.045 · DOI · Paper page
  33. Bishof, 2018, RNA-binding proteins with basic-acidic dipeptide (BAD) domains self-assemble and aggregate in Alzheimer's disease, J. Biol. Chem., 293, 11047, 10.1074/jbc.RA118.001747 · DOI · Paper page
  34. Jiang, 2019, TIA1 regulates the generation and response to toxic tau oligomers, Acta Neuropathol., 137, 259, 10.1007/s00401-018-1937-5 · DOI · Paper page
  35. Zhang, 2017, RNA stores tau reversibly in complex coacervates, PLoS Biol., 15, 10.1371/journal.pbio.2002183 · DOI · Paper page
  36. Weissmann, 1991, A 'unified theory' of prion propagation, Nature, 352, 679, 10.1038/352679a0 · DOI
  37. Burke, 2020, Cofactor and glycosylation preferences for in vitro prion conversion are predominantly determined by strain conformation, PLoS Pathog., 16, 10.1371/journal.ppat.1008495 · DOI
  38. Deleault, 2005, Protease-resistant prion protein amplification reconstituted with partially purified substrates and synthetic polyanions, J. Biol. Chem., 280, 26873, 10.1074/jbc.M503973200 · DOI
  39. Deleault, 2007, Formation of native prions from minimal components in vitro, Proc. Natl. Acad. Sci. U. S. A., 104, 9741, 10.1073/pnas.0702662104 · DOI
  40. Deleault, 2003, RNA molecules stimulate prion protein conversion, Nature, 425, 717, 10.1038/nature01979 · DOI
  41. Adler, 2003, Small, highly structured RNAs participate in the conversion of human recombinant PrP(Sen) to PrP(Res) in vitro, J. Mol. Biol., 332, 47, 10.1016/S0022-2836(03)00919-7 · DOI
  42. Saá, 2012, Strain-specific role of RNAs in prion replication, J. Virol., 86, 10494, 10.1128/JVI.01286-12 · DOI
  43. Gonzalez-Montalban, 2013, Changes in prion replication environment cause prion strain mutation, FASEB J, 27, 3702, 10.1096/fj.13-230466 · DOI
  44. Katorcha, 2018, Prion replication environment defines the fate of prion strain adaptation, PLoS Pathog., 14, 10.1371/journal.ppat.1007093 · DOI
  45. Hasegawa, 1997, Alzheimer-like changes in microtubule-associated protein Tau induced by sulfated glycosaminoglycans. Inhibition of microtubule binding, stimulation of phosphorylation, and filament assembly depend on the degree of sulfation, J. Biol. Chem., 272, 33118, 10.1074/jbc.272.52.33118 · DOI
  46. Wang, 2006, The proline-rich domain and the microtubule binding domain of protein tau acting as RNA binding domains, Protein Pept. Lett., 13, 679, 10.2174/092986606777790566 · DOI
  47. Dinkel, 2015, RNA binds to tau fibrils and sustains template-assisted growth, Biochemistry, 54, 4731, 10.1021/acs.biochem.5b00453 · DOI
  48. Carlson, 2007, A complex mechanism for inducer mediated tau polymerization, Biochemistry, 46, 8838, 10.1021/bi700403a · DOI
  49. Jiang, 2020, Tau oligomers and fibrils exhibit differential patterns of seeding and association with RNA binding proteins, Front. Neurol., 11, 579434, 10.3389/fneur.2020.579434 · DOI
  50. Goedert, 1992, Tau proteins of alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms, Neuron, 8, 159, 10.1016/0896-6273(92)90117-V · DOI

Cited by

See all 45

Metadata

Authors
Zwierzchowski-Zarate, A. N., Mendoza-Oliva, A., Kashmer, O. M., Collazo-Lopez, J. E., White, C. L., & Diamond, M. I.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2022-08
Volume
298
Issue
8
Pages
102132
ISSN
0021-9258
DOI
10.1016/j.jbc.2022.102132
PMC
PMC9364032
Cited by
45
References
21
Language
en
Licence
Funders
  • Chan Zuckerberg Initiative
  • National Institutes of Health
  • National Institute on Aging (1R01AG059689)

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: RNA induces unique tau strains and stabilizes Alzheimer’s disease seeds. https://app.cochat.ai/papers/10.1016/j.jbc.2022.102132
The paper
Zwierzchowski-Zarate, A. N., Mendoza-Oliva, A., Kashmer, O. M., Collazo-Lopez, J. E., White, C. L., & Diamond, M. I. (2022). RNA induces unique tau strains and stabilizes Alzheimer’s disease seeds. Journal of Biological Chemistry. https://doi.org/10.1016/j.jbc.2022.102132

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.