Affinage

MAPT

Microtubule-associated protein tau · UniProt P10636

Round 2 corrected
Length
758 aa
Mass
78.9 kDa
Annotated
2026-04-28
130 papers in source corpus 44 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAPT encodes tau, an intrinsically disordered microtubule-associated protein that promotes tubulin polymerization, suppresses microtubule catastrophe, and stabilizes dynamic instability—activities regulated by phosphorylation (GSK-3β, Cdk5, TTBK1), acetylation (p300/HDAC6), and competition with cofilin for microtubule binding (PMID:1057175, PMID:1421571, PMID:30911686, PMID:29734651). Beyond cytoskeletal regulation, tau targets Fyn kinase to postsynaptic NMDA receptors to modulate excitotoxic signaling, undergoes liquid–liquid phase separation with chromatin components to compact nucleosomes and regulate gene expression (e.g., VGluT1), and is secreted via Rab7A-dependent late endosomal pathways in an activity-dependent manner (PMID:20655099, PMID:38429335, PMID:30664870, PMID:28222213, PMID:27322420). Tau is the principal component of Alzheimer's disease paired helical filaments, and MAPT mutations cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) through a combination of reduced microtubule-binding capacity, altered exon 10 splicing favoring four-repeat isoforms, and enhanced filament formation; misfolded tau seeds propagate as conformationally distinct strains, escape lysosomes via ESCRT-recruited nanoscale membrane damage, and nucleate cytosolic aggregation in a prion-like manner (PMID:3131773, PMID:9641683, PMID:24857020, PMID:38781206). Intracellular tau clearance depends on the autophagy–lysosome axis regulated by BAG3/SYNPO, retromer/VPS35, and selective ubiquitination by CHIP/STUB1, while extracellular tau is eliminated through AQP4-dependent glymphatic drainage (PMID:30744518, PMID:32960680, PMID:37330289, PMID:35212707).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1975 High

    The fundamental question of what drives microtubule assembly was answered by identifying tau as a heat-stable protein factor essential for tubulin polymerization, establishing its identity as a microtubule-associated protein.

    Evidence In vitro reconstitution of microtubule assembly from purified porcine brain tubulin and tau

    PMID:1057175

    Open questions at the time
    • Mechanism of tau–tubulin interaction at residue level unknown
    • In vivo relevance not yet demonstrated
  2. 1988 High

    The molecular identity of paired helical filaments—the ultrastructural hallmark of Alzheimer's neurofibrillary tangles—was resolved when cDNA cloning showed tau is their principal structural component, linking tau directly to neurodegeneration.

    Evidence cDNA library screening with probes derived from PHF core protein sequence; RNA blot confirmation

    PMID:3131773

    Open questions at the time
    • What drives tau from a soluble microtubule-stabilizer to an insoluble filament was unknown
    • Post-translational modifications of PHF-tau not yet mapped
  3. 1989 High

    The isoform complexity of tau was established by cloning six human brain isoforms differing in N-terminal inserts and the number of microtubule-binding repeats (3R vs 4R), with developmentally regulated expression patterns relevant to both normal function and disease.

    Evidence cDNA cloning, RNase protection assays, and isoform-specific immunostaining in human brain

    PMID:2484340 PMID:2498079

    Open questions at the time
    • Functional consequences of 3R vs 4R ratio imbalance not yet known
    • Splicing regulatory mechanism not characterized
  4. 1992 High

    Direct single-microtubule observation revealed that tau modulates dynamic instability by increasing polymerization rate and decreasing catastrophe frequency, and that MAP kinase–mediated phosphorylation reduces these activities by lowering microtubule affinity—establishing phosphorylation as a key regulatory switch.

    Evidence Dark-field microscopy of individual microtubules with purified tau ± MAP kinase phosphorylation in vitro

    PMID:1421571

    Open questions at the time
    • Which specific phosphorylation sites govern each parameter was unresolved
    • Kinase identity in vivo not established
  5. 1998 High

    The genetic basis of familial tauopathy was resolved when MAPT missense and splice-site mutations were identified as causative for FTDP-17; mechanistic studies showed that missense mutations reduce microtubule binding/assembly while intronic mutations shift splicing toward 4R isoforms by disrupting an exon 10 stem-loop.

    Evidence Sequencing of FTDP-17 families; in vitro microtubule assembly with recombinant mutant tau; RNA structural analysis

    PMID:9636220 PMID:9641683 PMID:9824291 PMID:9836646

    Open questions at the time
    • Whether loss-of-function alone or gain-of-toxic-function (aggregation) drives disease was debated
    • Structural basis of mutation effects on filament formation unknown
  6. 2000 High

    The gain-of-function dimension of FTDP-17 mutations was demonstrated when several missense mutations were shown to stimulate heparin-induced tau filament formation in vitro, complementing the earlier loss-of-function evidence and establishing a dual-mechanism model.

    Evidence In vitro heparin-induced filament assembly assays with multiple recombinant FTDP-17 mutant tau proteins

    PMID:10899436

    Open questions at the time
    • Relevance of heparin-induced fibrils to patient-derived filaments uncertain
    • Seeding/propagation mechanisms unknown
  7. 2002 High

    A temporal map of tau phosphorylation during tangle evolution was constructed, revealing that specific phospho-epitopes mark sequential stages (pre-tangle → intraneuronal NFT → extracellular NFT), establishing phosphorylation as both a biomarker and a mechanistic correlate of disease progression.

    Evidence Systematic immunostaining of AD brain with 11 phospho-tau antibodies correlated with Braak staging

    PMID:11837744

    Open questions at the time
    • Causal relationships between individual phosphorylation events and aggregation steps not established
    • Kinases responsible for each site in situ not identified
  8. 2005 High

    The dissociation between neurofibrillary tangles and neurodegeneration was demonstrated when suppressing tau expression in a repressible transgenic mouse restored memory and halted neuron loss despite persistent NFTs, establishing that soluble tau species (not tangles) drive toxicity.

    Evidence Tet-off repressible P301L tau transgenic mice; behavioral testing; neuron counting after tau suppression

    PMID:16020737

    Open questions at the time
    • Identity of the toxic soluble tau species unknown
    • Whether this applies to human disease uncertain
  9. 2010 High

    A non-cytoskeletal dendritic function for tau was uncovered: tau targets Fyn kinase to postsynaptic sites where Fyn phosphorylates NMDA receptor NR2B subunits, coupling tau to excitotoxic signaling and Aβ toxicity downstream.

    Evidence Truncated tau, tau KO, and APP23 cross transgenic mice; biochemical fractionation; peptide rescue of memory deficits

    PMID:20655099

    Open questions at the time
    • Whether tau–Fyn interaction is direct or scaffold-mediated in vivo not resolved
    • Tau's role in other postsynaptic signaling complexes unexplored
  10. 2014 High

    The prion-like strain concept was extended to tau when conformationally distinct tau aggregates were shown to propagate clonally in cell culture and produce distinguishable pathologies across three generations of inoculated transgenic mice, establishing that tau conformation encodes strain identity.

    Evidence Clonal propagation in HEK293 cells expressing tau repeat domain; serial inoculation into transgenic mice; immunopurification and strain reestablishment

    PMID:24857020

    Open questions at the time
    • Structural basis of strain differences at atomic resolution not yet available
    • Host factors determining strain selectivity unknown
  11. 2017 High

    The atomic architecture of tau filaments was revealed by cryo-EM structures at 3.4–3.5 Å from AD brain, showing that residues 306–378 form a combined cross-β/β-helix core with paired helical and straight filaments as ultrastructural polymorphs differing only in inter-protofilament packing.

    Evidence Cryo-electron microscopy of patient-derived tau filaments with atomic model building

    PMID:28678775

    Open questions at the time
    • How post-translational modifications alter filament core structure unknown
    • Filament nucleation mechanism not captured by static structure
  12. 2017 High

    Tau secretion was placed in a defined trafficking pathway when Rab7A was shown to regulate tau release through late endosomal compartments, and neuronal activity was demonstrated to stimulate both tau secretion and in vivo pathology propagation.

    Evidence Rab7A knockout/dominant-negative/constitutively-active in neurons and HeLa cells; optogenetic and chemogenetic neuronal stimulation with in vitro and in vivo readouts

    PMID:27322420 PMID:28222213

    Open questions at the time
    • Sorting signals directing tau into late endosomes undefined
    • Relative contribution of exosomal vs. free tau secretion unclear
  13. 2019 Medium

    Multiple clearance pathways converged on tau homeostasis: BAG3/SYNPO were shown to facilitate autophagy-lysosome degradation of phospho-tau at postsynaptic densities, retromer/VPS35 regulated autophagic resolution of tau aggregates, and β-arrestin2 oligomers impaired autophagy by inhibiting p62 self-interaction.

    Evidence shRNA knockdown of BAG3/SYNPO in neurons; VPS35 knockdown/overexpression in tau aggregation models; β-arrestin2 KO crossed with P301S mice

    PMID:30744518 PMID:32071246 PMID:32960680

    Open questions at the time
    • Integration of these pathways into a unified clearance hierarchy not established
    • Whether these mechanisms operate equivalently in human neurons untested
  14. 2021 High

    The E3 ubiquitin ligase CHIP/STUB1 was identified as a selective quality-control factor for phosphorylated tau, binding it ~10-fold more strongly than unmodified tau and suppressing its aggregation and seeding at sub-stoichiometric concentrations through rapid ubiquitination.

    Evidence In vitro binding screen, reconstituted ubiquitination assay, and cell-based seeding assay with phosphorylated tau substrate

    PMID:37330289

    Open questions at the time
    • In vivo significance for endogenous tau clearance not demonstrated
    • Proteasomal vs. autophagic fate of CHIP-ubiquitinated tau unclear
  15. 2024 High

    The mechanism of tau seed escape from the endolysosomal system was resolved: tau fibrils induce nanoscale (not wholesale) lysosomal membrane damage that recruits ESCRT machinery, and cytosolic tau nucleation occurs primarily at the damaged lysosomal membrane, coupling seed escape to aggregation initiation.

    Evidence STORM superresolution microscopy; ESCRT and Galectin-3 recruitment assays; live imaging in primary astrocytes and neurons

    PMID:38781206

    Open questions at the time
    • Whether ESCRT repair succeeds or fails in determining seeding outcome is unresolved
    • In vivo validation of lysosomal nucleation mechanism pending
  16. 2024 Medium

    A nuclear chromatin-regulatory function for tau was biochemically defined: tau undergoes LLPS with DNA, mononucleosomes, and nucleosome arrays, compacts chromatin, co-phase-separates with HP1α, and regulates gene expression (VGluT1); hyperphosphorylation disrupts this nuclear LLPS, suggesting loss of chromatin function in tauopathy.

    Evidence In vitro LLPS assays with reconstituted nucleosomes; DNase protection; co-phase-separation with HP1α; VGluT1 expression assays

    PMID:30664870 PMID:38429335

    Open questions at the time
    • Genome-wide transcriptional targets of nuclear tau unknown
    • In vivo chromatin occupancy sites not mapped
    • Relative contribution of nuclear tau loss-of-function to disease phenotype undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the toxic soluble tau species driving neurodegeneration, the structural basis of how post-translational modifications redirect tau from microtubule stabilization to aggregation or phase separation, and the mechanism by which conformational strain identity is faithfully propagated during trans-synaptic spreading in the human brain.
  • Toxic tau species (oligomer, monomer, modified form) not definitively identified
  • No integrative structural model links PTM patterns to conformational fate decisions
  • Strain propagation fidelity in human brain not validated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 6 GO:0005198 structural molecule activity 3 GO:0003677 DNA binding 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005856 cytoskeleton 5 GO:0005576 extracellular region 3 GO:0005634 nucleus 2 GO:0005764 lysosome 2 GO:0005768 endosome 2 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-1852241 Organelle biogenesis and maintenance 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9612973 Autophagy 3 R-HSA-112316 Neuronal System 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-4839726 Chromatin organization 1
Partners
ARRB2BIN1CFL1FYNLRP1STUB1TIA1VPS35

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1975 Tau (MAPT) was identified as a heat-stable protein factor essential for microtubule assembly in vitro. In the absence of tau, tubulin 6S dimers do not polymerize; addition of tau completely restores tubule-forming capacity and converts 6S dimers to 36S rings implicated as polymerization intermediates. In vitro microtubule assembly reconstitution with purified porcine brain tau and tubulin; ion exchange chromatography separation Proceedings of the National Academy of Sciences of the United States of America High 1057175
1988 Tau protein (encoded by MAPT) was identified as a core component of the paired helical filaments (PHFs) of Alzheimer's disease neurofibrillary tangles by cDNA cloning and sequencing, establishing tau as the major structural constituent of NFTs. cDNA library screening with oligonucleotide probes derived from PHF core protein partial sequence; RNA blot analysis; sequence homology to mouse tau Proceedings of the National Academy of Sciences of the United States of America High 3131773
1989 Human MAPT undergoes alternative splicing to produce multiple tau isoforms differing by insertions of 29 or 58 amino acids in the N-terminal region and by inclusion of three or four microtubule-binding repeats. The four-repeat isoform and the N-terminal insert isoforms are expressed in an adult-specific manner, whereas the three-repeat isoform is expressed throughout life including fetal brain. All isoforms are incorporated into Alzheimer's disease neurofibrillary tangles. cDNA cloning, RNase protection assays, immunostaining with isoform-specific antisera raised against synthetic peptides Neuron High 2484340
1989 A four-repeat tau isoform (383 aa) encoded by an additional exon was cloned and shown to be expressed in an adult- and cell-specific manner in human brain; both three- and four-repeat tau isoforms are present in the PHF core of Alzheimer's disease neurofibrillary tangles. cDNA cloning, RNA blot analysis, in situ hybridization, immunostaining The EMBO journal High 2498079
1992 Tau modulates microtubule dynamic instability by increasing the rate of polymerization, decreasing the catastrophe rate, and inhibiting depolymerization. Phosphorylation by MAP kinase perturbs all three activities by lowering tau's affinity for the microtubule lattice. Direct dark-field microscopy observation of individual microtubule dynamics in vitro; kinetic analysis with purified tau; in vitro phosphorylation assay Molecular biology of the cell High 1421571
1998 Missense mutations in MAPT (G272V, P301L, R406W) and mutations in the 5' splice site of exon 10 cause FTDP-17. Splice-site mutations destabilize a stem-loop structure regulating exon 10 alternative splicing, increasing the proportion of four-repeat tau isoforms. DNA sequencing of MAPT in FTDP-17 families; RNA structural analysis of splice-site mutations; segregation analysis Nature High 9641683
1998 A G-to-A intronic mutation after exon 10 of MAPT in familial MSTD/FTDP-17 disrupts a predicted stem-loop structure at the 3' end of the splice-donor site, leading to abnormal preponderance of four-repeat tau isoforms in soluble and insoluble tau fractions. DNA sequencing, RNA structural prediction, biochemical isoform analysis of sarkosyl-insoluble tau fractions Proceedings of the National Academy of Sciences of the United States of America High 9636220
1998 FTDP-17 missense mutations G272V, P301L, V337M, and R406W in tau markedly reduce the ability of tau to promote microtubule assembly in vitro, demonstrating a partial loss-of-function as the primary effect of these mutations. In vitro microtubule assembly assay with recombinant mutant tau proteins; turbidimetry FEBS letters High 9824291
1998 Functional analyses of FTDP-17 missense mutations showed that most reduce tau's ability to bind microtubules and promote assembly. Different mutations differentially alter distinct biochemical properties and stoichiometry of tau isoforms. In sarkosyl-insoluble fractions from patient brains, specific mutations produce distinct isoform compositions. Recombinant tau functional assays (microtubule binding and assembly); biochemical analysis of sarkosyl-insoluble tau from patient brains Science High 9836646
2000 FTDP-17 mutations produce either reduced ability of tau to interact with microtubules, or overproduction of four-repeat tau isoforms; several missense mutations also stimulate heparin-induced tau filament formation in vitro, suggesting that assembly of tau into filaments represents a gain of toxic function. In vitro microtubule binding assays; heparin-induced tau filament assembly assays with recombinant mutant tau Biochimica et biophysica acta High 10899436
2001 GSK-3β controls tau phosphorylation and tau's functional interaction with microtubules. In transfected cells and cultured neurons, GSK-3β activity governs tau phosphorylation state; in NFT-bearing neurons, acetylated α-tubulin immunoreactivity (marker of stable microtubules) is strongly reduced, consistent with microtubule destabilization caused by phosphorylated tau. Transfected cell assays; cultured neuron experiments; immunohistochemistry; in situ hybridization Biochemical Society symposium Medium 11447842
2002 Specific tau phosphorylation sites correlate with sequential stages of neurofibrillary tangle development in AD: TG3 (pT231), pS262, and pT153 mark the pre-tangle state; pT175/181, 12E8 (pS262/S356), pS422, pS46, pS214 mark intraneuronal NFTs; AT8 (pS199/S202/T205), AT100 (pT212/S214), and PHF-1 (pS396/S404) are most prominent in extracellular NFTs, defining a temporal sequence of phosphorylation events during neuronal cytopathology. Systematic immunostaining with 11 phosphorylation-dependent tau antibodies on a panel of AD cases; correlation with tangle stage Acta neuropathologica High 11837744
2005 Transglutaminase cross-links phosphorylated tau in vivo. In P301L tau transgenic mice that develop NFTs, transglutaminase cross-links phosphorylated tau into high-molecular-mass aggregates, with transglutaminase enzymatic activity significantly elevated in the spinal cord; this cross-linking co-localizes with PHF-1-immunoreactive tau in neurons. Immunoprecipitation, immunoblotting, double-label immunofluorescence, enzymatic activity assay in transgenic mouse brain The Journal of neuroscience Medium 15689560
2006 FTDP-17 mutations G272V, ΔK280, and P301L markedly reduce the ability of tau to regulate microtubule dynamic instability in living cells, while R406W (outside the microtubule-binding domain) does not significantly alter microtubule regulation, supporting a loss-of-function model for these mutations. Microinjection of recombinant wild-type and mutant tau into cells expressing fluorescent tubulin; direct measurement of individual microtubule dynamic instability parameters The Journal of biological chemistry High 16495230
2007 In P301S tau transgenic mice, hippocampal synapse loss and impaired synaptic function precede fibrillary tau tangle formation (detected at 3 months before 6-month tangle onset), and prominent microglial activation also precedes tangles. Immunosuppression with FK506 attenuated tau pathology and increased lifespan, linking neuroinflammation to early tauopathy progression. Transgenic mouse model analysis; electrophysiology; immunohistochemistry; FK506 pharmacological intervention Neuron High 17270732
2005 Tau suppression in mice expressing a repressible P301L human tau restored memory function and stabilized neuron numbers after NFT formation, demonstrating that NFTs per se are not sufficient to cause cognitive decline or neuronal death, and that ongoing tau expression (not NFTs) drives these deficits. Tet-off repressible transgenic mouse model; behavioral testing; immunohistochemistry; neuron counting Science High 16020737
2009 FTDP-17 missense mutations G272V, P301L, V337M, and R406W promote phosphorylation of tau at Ser202 by Cdk5 in vitro, and this Ser202 phosphorylation inhibits tau's microtubule assembly-promoting activity more severely in mutant tau than in wild-type tau. In vitro Cdk5 phosphorylation of recombinant mutant tau; microtubule assembly assay; SDS-PAGE mobility shift analysis The Journal of biological chemistry High 19304664
2010 Tau has a dendritic function: it targets the Src kinase Fyn to postsynaptic compartments, where Fyn phosphorylates NR2B subunit of NMDA receptors and promotes interaction with PSD-95. Missorting of tau (by truncation) or tau deficiency disrupts postsynaptic Fyn targeting, uncouples NMDA receptor-mediated excitotoxicity, and mitigates Aβ toxicity in APP23 mice. A peptide uncoupling Fyn-NR2B-PSD-95 interaction fully rescues memory deficits. Transgenic mouse models (truncated tau, tau knockout, APP23 crosses); behavioral testing; biochemical fractionation; peptide rescue experiments Cell High 20655099
2011 When tau expression exceeds an intracellular threshold in non-neuronal cells, tau is released to the extracellular medium in association with membrane vesicles (exosomes), suggesting a cellular mechanism to eliminate excess tau protein. Tau overexpression in non-neuronal cells; biochemical fractionation; detection of tau in conditioned medium associated with membrane vesicles FEBS letters Medium 22138183
2012 Aggregated (but not monomeric) tau inhibits anterograde fast axonal transport (FAT) in squid axoplasm. This inhibition requires a small N-terminal phosphatase-activation domain (PAD). Hsp70 preferentially binds tau oligomers over filaments and prevents the FAT inhibition caused by aggregated tau mixtures. Squid axoplasm perfusion assay; antibody labeling with PAD-specific (TNT1) and oligomer-specific (TOC1) antibodies; Hsp70 rescue experiment Biochemical Society transactions Medium 22817713
2014 Tau acetylation by p300 histone acetyltransferase (HAT) disfavors liquid-liquid phase separation (LLPS), inhibits heparin-induced aggregation, and impedes LLPS-initiated microtubule assembly, suggesting that hyperacetylation contributes to tau loss-of-function by preventing LLPS-mediated microtubule assembly. In vitro hyperacetylation of tau by p300 HAT; ThT aggregation assay; phase separation assay; microtubule assembly assay International journal of molecular sciences Medium 29734651
2014 HDAC6 functions as a tau deacetylase; inhibition of HDAC6 has neuroprotective effects including microtubule stabilization in tau-based pathologies. Review of experimental evidence for HDAC6 as tau deacetylase; pharmacological HDAC6 inhibition studies in tau models Alzheimer's research & therapy Medium 25031639
2014 Tau strains stably propagate distinct amyloid conformations in a clonal fashion in cultured cells; reintroduction of tau from these lines into naive cells reestablishes identical clones. Two strains produced in vitro induce distinct pathologies in vivo across three generations of transgenic mice, demonstrating that tau conformation encodes strain identity analogous to prions. Stable tau repeat domain expression in HEK293 cells; clonal propagation assays; inoculation of tau strains into transgenic mice; immunopurification and strain reestablishment in culture Neuron High 24857020
2016 Neuronal activity stimulates tau release from cells in vitro and enhances tau pathology in vivo. Using optogenetic and chemogenetic approaches to increase neuronal activity, both tau secretion and tau pathology (seeding/propagation) were enhanced, demonstrating activity-dependent regulation of tau release. Optogenetic and chemogenetic manipulation of neuronal activity; in vitro tau secretion assay; in vivo tau pathology quantification in transgenic mice Nature neuroscience High 27322420
2017 Cryo-EM structures of tau filaments from Alzheimer's disease brain at 3.4–3.5 Å resolution show that filament cores are made of two identical protofilaments comprising residues 306–378 of tau, adopting a combined cross-β/β-helix structure. Paired helical and straight filaments differ only in inter-protofilament packing, making them ultrastructural polymorphs. This defines the seed structure for tau aggregation. Cryo-electron microscopy of patient-derived tau filaments; atomic model building Nature High 28678775
2017 Rab7A regulates tau secretion: deletion of Rab7A decreases tau secretion, while a constitutively active Rab7A increases it. A dominant-negative Rab7A also decreases secretion, and tau co-localizes with Rab7-positive late endosomal structures, indicating a late endosomal compartment is involved in tau secretion. Rab7A knockout, dominant-negative and constitutively active expression in primary cortical neurons and HeLa cells overexpressing tau; tau secretion assays; co-localization imaging Journal of neurochemistry Medium 28222213
2017 FTDP-17 tau mutations act to enhance phosphorylation of tau in vivo in Drosophila, and phosphorylation-dependent excess stabilization of the actin cytoskeleton is a key downstream mediator of tau neurotoxicity. Autophagy and the unfolded protein response are co-regulated with this cytoskeletal stabilization. Site-directed insertion transgenic Drosophila expressing wild-type and five FTDP-17 mutant human tau isoforms; neurodegeneration markers; actin cytoskeleton analysis; autophagy and UPR pathway analysis The Journal of neuroscience Medium 29138281
2018 Tau directly interacts with BIN1 through BIN1's SH3 domain and the tau proline-rich motif P216PTPR221. NMR-based structural modeling revealed key contacts (P216, P219 with BIN1 aromatic residues; R221, K224 with BIN1 acidic residues). Phosphorylation of tau at T212, T217, T231, and S235 reduces BIN1 SH3 affinity 5-fold and prevents tau from competing with the BIN1 intramolecular SH3-CLAP interaction. Nuclear magnetic resonance spectroscopy; structural modeling; affinity measurements (Kd); competitive binding assays with phosphorylated vs. unphosphorylated tau peptides Frontiers in molecular neuroscience High 30487734
2019 BAG3 (co-chaperone) cooperates with SYNPO (synaptopodin) to facilitate autophagic clearance of phospho-MAPT (pSer262) in neuronal processes. Loss of either BAG3 or SYNPO impedes autophagosome-lysosome fusion predominantly in the post-synaptic compartment, causing accumulation of SQSTM1/p62 and pSer262-tau in autophagosomes at post-synaptic densities. shRNA knockdown of BAG3 and SYNPO in mature neurons (20-24 DIV); immunofluorescence; autophagy flux assays; co-localization with autophagy markers Autophagy Medium 30744518
2019 Cofilin competes with tau for direct microtubule binding in vitro, in cells, and in vivo, inhibiting tau-induced microtubule assembly. Genetic reduction of cofilin mitigates tauopathy and synaptic defects in Tau-P301S mice and movement deficits in tau transgenic C. elegans. Only activated (dephosphorylated) cofilin selectively interacts with tubulin, destabilizes microtubules, and promotes tauopathy. In vitro microtubule co-sedimentation; cell-based microtubule assays; genetic cofilin reduction in P301S mice; tau transgenic C. elegans behavioral assays Communications biology High 30911686
2019 LRRK2 acts as a scaffold facilitating tau phosphorylation rather than as a direct tau kinase: LRRK2 binds tau 140–200-fold more strongly than cdk5 but phosphorylates tau with 250–480-fold lower specific activity than cdk5. cdk5 and tau co-immunoprecipitate with endogenous LRRK2 in cells and mouse brain. LRRK2 knockdown reduces tau phosphorylation at Ser396/404, while LRRK2 kinase inhibition has no effect on these sites. In vitro kinase assays with LRRK2 and cdk5; co-immunoprecipitation from SH-SY5Y cells, mouse brain, and human PBMCs; siRNA knockdown; pharmacological kinase inhibition; overexpression of kinase-dead mutant Biochemistry Medium 26268594
2019 TTBK1 (Tau-tubulin kinase 1) directly phosphorylates tau at Ser422 and activates CDK5, a major tau kinase, promoting tau accumulation and aggregation. TTBK1 is specifically expressed in the CNS, and its transgenic overexpression accelerates tau accumulation and neuroinflammation in tau mutant mice. In vitro kinase assay; CDK5 activation assay; TTBK1 transgenic mice crossed with P301L tau mice; immunohistochemistry Frontiers in molecular neuroscience Medium 24808823
2020 β-Arrestin2 oligomers stabilize pathogenic tau and promote tau aggregation via non-GPCR mechanisms. Oligomerized (but not monomeric) β-arrestin2 inhibits self-interaction of the autophagy cargo receptor p62/SQSTM1, thereby impeding autophagy flux and tau clearance. Genetic ablation of β-arrestin2 markedly reduces tau pathology and rescues synaptic plasticity in P301S tau mice. Atomic force microscopy; defined mutant β-arrestin2 constructs; KO and overexpression in cells and primary neurons; P301S × β-arrestin2−/− cross; AAV-encoded dominant-negative in vivo Proceedings of the National Academy of Sciences of the United States of America High 32071246
2020 LRP1 is an endocytic receptor for tau: it binds monomeric tau and the tau microtubule-binding domain with high affinity (surface plasmon resonance), rapidly internalizes tau, and delivers it to lysosomes for degradation. Phosphorylated tau binds LRP1 weakly and is less efficiently internalized. ApoE (especially apoE4) inhibits LRP1-mediated tau uptake. LRP1-expressing (but not LRP1-deficient) cells promote cytosolic tau seeding from pathological brain-derived tau. Surface plasmon resonance; 125I-labeled tau internalization assay; lysosomal degradation assay; cell lines with/without LRP1; tau seeding assay with AD brain lysates The Journal of biological chemistry High 33930462
2020 Retromer (specifically the VPS35 component) regulates autophagy-lysosomal clearance of MAPT aggregates. VPS35 depletion blocks autophagy resolution and causes marked accumulation of cytoplasmic MAPT aggregates; VPS35 overexpression has the opposite effect. Chemical and genetic autophagy blockade; VPS35 knockdown and overexpression in cell models of tau aggregation; biochemical aggregation assays Autophagy Medium 32960680
2020 AQP4 (aquaporin-4)-driven glymphatic clearance facilitates elimination of extracellular tau from brain interstitial fluid to CSF and cervical lymph nodes. AQP4 deletion elevates CSF tau and markedly exacerbates phosphorylated tau deposition and neurodegeneration in P301S tau transgenic mice. AQP4 knockout mice crossed with P301S tau transgenic mice; tau measurement in CSF and lymph nodes; phospho-tau immunohistochemistry; neurodegeneration scoring The Journal of experimental medicine High 35212707
2021 TIA1 (RNA-binding protein) interaction with tau and RNA is sufficient to drive tau phase separation at physiological concentrations without artificial crowding agents. Phase separation of tau with TIA1 generates tau oligomers that are significantly more toxic than tau aggregates generated by RNA alone or artificial crowding, identifying a new source of toxic oligomers. In vitro phase separation assay with recombinant tau, RNA, and TIA1; oligomer characterization; cell toxicity assays; comparison with G3BP1 and crowding agent conditions Proceedings of the National Academy of Sciences of the United States of America High 33619090
2021 Tau forms small oligomeric complexes on microtubules in cells under physiological conditions, distinct from pathological tau aggregates. Single-molecule localization microscopy showed that distinct tau phosphorylation states are associated with different tau aggregate morphologies. Single-molecule localization microscopy (STORM/SMLM); unsupervised shape classification algorithm; ex vivo neuronal preparations Proceedings of the National Academy of Sciences of the United States of America Medium 33952699
2021 CHIP/STUB1 (E3 ubiquitin ligase) selectively binds phosphorylated tau ~10-fold more strongly than unmodified tau via its TPR domain. Sub-stoichiometric CHIP strongly suppresses aggregation and seeding of phosphorylated tau, promotes rapid ubiquitination of phosphorylated (but not unmodified) tau in vitro, and restricts tau seeding in cells. Binding screen of TPR-domain chaperones; in vitro ubiquitination assay; aggregation and seeding assays; cell-based seeding assay Journal of molecular biology High 37330289
2021 PIKfyve activity is required for lysosomal trafficking of tau seeds and subsequent tau seeding in neurons. Dynamin-1, actin, and Rac1 are key players in tau seed endocytosis. PIKfyve inhibition (pharmacological and genetic), downstream of Rac1, reduces tau seed trafficking to lysosomes and inhibits induction of tau aggregation. Pharmacological inhibition and genetic tools (siRNA); endocytic pathway analysis; tau seeding assay in neurons The Journal of biological chemistry Medium 33831417
2021 Tau acetylmimetics at K321 and K353 (within KXGS motifs) strongly inhibit prion-like seeded aggregation of pathogenic P301L tau and impair intrinsic aggregation of P301L/S320F tau, altering tau conformation to extensively block Thioflavin S binding. All KXGS acetylmimetics reduce tau-microtubule interactions. HEK293T transfection of acetylmimetic (K→Q) tau mutants; microtubule binding assay; prion-like seeded aggregation assay; Thioflavin S binding Scientific reports Medium 34426645
2024 Tau fibrils induce nanoscale lysosomal membrane damage upon endocytosis in primary astrocytes and neurons, recruiting ESCRT proteins (but not Galectin-3), indicating nanoscale rather than wholesale membrane rupture. Nucleation of cytosolic tau occurs primarily at the lysosomal membrane, coupling lysosomal escape to initiation of tau seeding. Live cell imaging; STORM superresolution microscopy; ESCRT and Galectin-3 recruitment assays; lysosomal swelling and deacidification measurements in primary astrocytes and neurons Proceedings of the National Academy of Sciences of the United States of America High 38781206
2024 Tau undergoes liquid-liquid phase separation (LLPS) with DNA, mononucleosomes, and reconstituted nucleosome arrays under low salt conditions. Low concentrations of tau promote chromatin compaction and protect DNA from digestion; tau co-localizes into droplets with nucleosome arrays and phosphorylated HP1α. Aberrant hyperphosphorylation disrupts tau LLPS with chromatin, suggesting loss of nuclear chromatin regulatory function in tauopathy. In vitro biophysical LLPS assays with recombinant tau, DNA, and reconstituted nucleosomes; DNase protection assay; co-phase separation with HP1α; hyperphosphorylated tau comparison Communications biology Medium 38429335
2019 A small amount of tau localizes in the nuclear compartment (in both soluble and chromatin-bound fractions). Favoring tau nuclear translocation by overexpression or detachment from microtubules increases VGluT1 (vesicular glutamate transporter 1) gene expression. The P301L FTDP-17 mutation impairs this nuclear function, representing a loss-of-function mechanism distinct from aggregation. Subcellular fractionation; live imaging; tau overexpression and microtubule detachment; VGluT1 expression quantification; P301L mutant comparison Journal of molecular biology Medium 30664870

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 2851 9641683
1975 A protein factor essential for microtubule assembly. Proceedings of the National Academy of Sciences of the United States of America 2732 1057175
2006 TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochemical and biophysical research communications 2242 17084815
1989 Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron 2108 2484340
2007 Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 1831 17270732
2014 Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA neurology 1686 24493463
2005 Tau suppression in a neurodegenerative mouse model improves memory function. Science (New York, N.Y.) 1599 16020737
2017 Cryo-EM structures of tau filaments from Alzheimer's disease. Nature 1572 28678775
2009 Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nature genetics 1562 19915575
2014 Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nature genetics 1512 25064009
2010 Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell 1512 20655099
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1998 Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proceedings of the National Academy of Sciences of the United States of America 1243 9636220
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
1998 Tau is a candidate gene for chromosome 17 frontotemporal dementia. Annals of neurology 1144 9629852
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2018 Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature 1015 30232451
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nature genetics 958 22504420
2020 Plasma P-tau181 in Alzheimer's disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer's dementia. Nature medicine 950 32123385
1988 Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proceedings of the National Academy of Sciences of the United States of America 938 3131773
2013 Tau pathology and neurodegeneration. The Lancet. Neurology 888 23684085
1989 Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain. The EMBO journal 879 2498079
2002 Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer's disease. Acta neuropathologica 832 11837744
1992 Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau. Molecular biology of the cell 806 1421571
1998 Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17. Science (New York, N.Y.) 805 9836646
2012 Trans-synaptic spread of tau pathology in vivo. PloS one 802 22312444
2010 Tau in Alzheimer disease and related tauopathies. Current Alzheimer research 796 20678074
2014 Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron 790 24857020
2011 The many faces of tau. Neuron 676 21555069
2016 Neuronal activity enhances tau propagation and tau pathology in vivo. Nature neuroscience 648 27322420
2016 Tau and tauopathies. Brain research bulletin 458 27615390
1998 Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly. FEBS letters 397 9824291
2011 Neuropathology of frontotemporal lobar degeneration-tau (FTLD-tau). Journal of molecular neuroscience : MN 308 21720721
2004 The role of tau (MAPT) in frontotemporal dementia and related tauopathies. Human mutation 277 15365985
2021 Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation. Frontiers in neurology 271 33488497
2019 A walk through tau therapeutic strategies. Acta neuropathologica communications 211 30767766
2022 Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration. The Journal of experimental medicine 200 35212707
2012 Tau oligomers and tau toxicity in neurodegenerative disease. Biochemical Society transactions 179 22817713
2018 Biomarkers for tau pathology. Molecular and cellular neurosciences 173 30529601
2018 Tau in neurodegenerative disease. Annals of translational medicine 164 29951497
2017 Propagation of Tau aggregates. Molecular brain 154 28558799
2018 Acetylation Disfavors Tau Phase Separation. International journal of molecular sciences 144 29734651
2018 It's all about tau. Progress in neurobiology 139 30605723
2019 Prevention of tau seeding and propagation by immunotherapy with a central tau epitope antibody. Brain : a journal of neurology 135 31038156
2012 Tau and tauopathies. Progress in molecular biology and translational science 133 22482453
2000 Tau mutations in frontotemporal dementia FTDP-17 and their relevance for Alzheimer's disease. Biochimica et biophysica acta 131 10899436
2017 Tau passive immunization inhibits not only tau but also Aβ pathology. Alzheimer's research & therapy 129 28073379
2011 Proteostasis of tau. Tau overexpression results in its secretion via membrane vesicles. FEBS letters 129 22138183
2016 Tau Biology and Tau-Directed Therapies for Alzheimer's Disease. Drugs 126 26729186
2021 TIA1 potentiates tau phase separation and promotes generation of toxic oligomeric tau. Proceedings of the National Academy of Sciences of the United States of America 118 33619090
2018 Retiring the term FTDP-17 as MAPT mutations are genetic forms of sporadic frontotemporal tauopathies. Brain : a journal of neurology 116 29253099
2020 Toxic tau: structural origins of tau aggregation in Alzheimer's disease. Neural regeneration research 111 31997800
2021 Tau Oligomers Neurotoxicity. Life (Basel, Switzerland) 109 33418848
2016 Tau Structures. Frontiers in aging neuroscience 108 27877124
2017 Amyloidogenesis of Tau protein. Protein science : a publication of the Protein Society 106 28833749
2014 Acetylation: a new key to unlock tau's role in neurodegeneration. Alzheimer's research & therapy 105 25031639
2021 Tau strains shape disease. Acta neuropathologica 104 33830330
2005 Pathways of tau fibrillization. Biochimica et biophysica acta 103 15615636
2010 Proteolytic processing of tau. Biochemical Society transactions 100 20658984
2018 Tau filaments in neurodegenerative diseases. FEBS letters 99 29790176
2021 Regulation of tau internalization, degradation, and seeding by LRP1 reveals multiple pathways for tau catabolism. The Journal of biological chemistry 97 33930462
2001 Neurofibrillary tangles and tau phosphorylation. Biochemical Society symposium 89 11447842
2010 From tau phosphorylation to tau aggregation: what about neuronal death? Biochemical Society transactions 88 20658986
2020 Resurrecting the Mysteries of Big Tau. Trends in neurosciences 84 32434664
2018 Different tau species lead to heterogeneous tau pathology propagation and misfolding. Acta neuropathologica communications 83 30497516
2006 FTDP-17 mutations compromise the ability of tau to regulate microtubule dynamics in cells. The Journal of biological chemistry 81 16495230
2020 Human tau pathology transmits glial tau aggregates in the absence of neuronal tau. The Journal of experimental medicine 79 31826239
2013 Anesthesia and tau pathology. Progress in neuro-psychopharmacology & biological psychiatry 78 23535147
2019 BAG3 and SYNPO (synaptopodin) facilitate phospho-MAPT/Tau degradation via autophagy in neuronal processes. Autophagy 76 30744518
2022 Tau Isoforms: Gaining Insight into MAPT Alternative Splicing. International journal of molecular sciences 75 36499709
2013 What Renders TAU Toxic. Frontiers in neurology 70 23772223
2021 Tau forms oligomeric complexes on microtubules that are distinct from tau aggregates. Proceedings of the National Academy of Sciences of the United States of America 69 33952699
2008 Tau oligomerization: a role for tau aggregation intermediates linked to neurodegeneration. Current Alzheimer research 67 19075586
2013 Characteristics of tau oligomers. Frontiers in neurology 65 23882258
2013 Tauopathies and tau oligomers. Journal of Alzheimer's disease : JAD 65 23948895
2018 Aging-related tau astrogliopathy (ARTAG): not only tau phosphorylation in astrocytes. Brain pathology (Zurich, Switzerland) 64 29396893
2021 Human Tau Isoforms and Proteolysis for Production of Toxic Tau Fragments in Neurodegeneration. Frontiers in neuroscience 60 34744602
2020 Bacterial DNA promotes Tau aggregation. Scientific reports 57 32047247
2014 Tau-tubulin kinase. Frontiers in molecular neuroscience 56 24808823
2024 Tau fibrils induce nanoscale membrane damage and nucleate cytosolic tau at lysosomes. Proceedings of the National Academy of Sciences of the United States of America 54 38781206
2019 Activated cofilin exacerbates tau pathology by impairing tau-mediated microtubule dynamics. Communications biology 54 30911686
2021 Tau and MAPT genetics in tauopathies and synucleinopathies. Parkinsonism & related disorders 53 34593302
2015 The many faces of interferon tau. Amino acids 53 25557050
2017 Rab7A regulates tau secretion. Journal of neurochemistry 52 28222213
2020 α-Linolenic acid inhibits Tau aggregation and modulates Tau conformation. International journal of biological macromolecules 51 33130263
2016 17q21.31 duplication causes prominent tau-related dementia with increased MAPT expression. Molecular psychiatry 51 27956742
2010 Tau cleavage and tau aggregation in neurodegenerative disease. Biochemical Society transactions 51 20658996
2013 Intercellular transfer of tau aggregates and spreading of tau pathology: Implications for therapeutic strategies. Neuropharmacology 48 24050961
2015 Tau Immunotherapy. Neuro-degenerative diseases 46 26551002
2020 Long non-coding RNA 00507/miRNA-181c-5p/TTBK1/MAPT axis regulates tau hyperphosphorylation in Alzheimer's disease. The journal of gene medicine 45 32891070
2019 Association of MAPT Subhaplotypes With Risk of Progressive Supranuclear Palsy and Severity of Tau Pathology. JAMA neurology 45 30882841
2018 Zinc Exacerbates Tau Pathology in a Tau Mouse Model. Journal of Alzheimer's disease : JAD 43 29914030
2019 Tau-Cofactor Complexes as Building Blocks of Tau Fibrils. Frontiers in neuroscience 42 31920504
2013 Hypoglycemia induces tau hyperphosphorylation. Current Alzheimer research 42 23036024
2022 Tau Aggregation. Neuroscience 41 35525497
2020 β-Arrestin2 oligomers impair the clearance of pathological tau and increase tau aggregates. Proceedings of the National Academy of Sciences of the United States of America 41 32071246
2009 Familial FTDP-17 missense mutations inhibit microtubule assembly-promoting activity of tau by increasing phosphorylation at Ser202 in vitro. The Journal of biological chemistry 41 19304664
2023 Tau and neurodegeneration. Cytoskeleton (Hoboken, N.J.) 40 38073060
2014 Memory deficits correlate with tau and spine pathology in P301S MAPT transgenic mice. Neuropathology and applied neurobiology 39 24865638
2008 Tau aggregates and tau pathology. Journal of Alzheimer's disease : JAD 39 18688097
2014 Annonacin, a natural lipophilic mitochondrial complex I inhibitor, increases phosphorylation of tau in the brain of FTDP-17 transgenic mice. Experimental neurology 38 24389273
1999 Fibrillogenesis of tau: insights from tau missense mutations in FTDP-17. Brain pathology (Zurich, Switzerland) 38 10517508
2022 Tau Toxicity in Neurodegeneration. Molecular neurobiology 37 35359226
2015 Azaphilones inhibit tau aggregation and dissolve tau aggregates in vitro. ACS chemical neuroscience 37 25822288
2005 Tau protein is cross-linked by transglutaminase in P301L tau transgenic mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 37 15689560
2018 Structural Basis of Tau Interaction With BIN1 and Regulation by Tau Phosphorylation. Frontiers in molecular neuroscience 36 30487734
2021 Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state. Brain : a journal of neurology 35 33842937
2021 Tau internalization: A complex step in tau propagation. Ageing research reviews 33 33571704
2019 14-3-3/Tau Interaction and Tau Amyloidogenesis. Journal of molecular neuroscience : MN 33 31062171
2022 All the Tau We Cannot See. Annual review of medicine 32 36378913
2024 Phosphorylation regulates tau's phase separation behavior and interactions with chromatin. Communications biology 31 38429335
2021 PIKfyve activity is required for lysosomal trafficking of tau aggregates and tau seeding. The Journal of biological chemistry 31 33831417
2020 Retromer regulates the lysosomal clearance of MAPT/tau. Autophagy 31 32960680
2015 Rescue from tau-induced neuronal dysfunction produces insoluble tau oligomers. Scientific reports 31 26608845
2017 A Conserved Cytoskeletal Signaling Cascade Mediates Neurotoxicity of FTDP-17 Tau Mutations In Vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 29138281
2005 The effect of tau genotype on clinical features in FTDP-17. Parkinsonism & related disorders 29 15878580
2018 Effects of Resveratrol and Morin on Insoluble Tau in Tau Transgenic Mice. Translational neuroscience 28 30479844
2016 Pioglitazone prevents tau oligomerization. Biochemical and biophysical research communications 28 27543203
2020 Red Ginseng Inhibits Tau Aggregation and Promotes Tau Dissociation In Vitro. Oxidative medicine and cellular longevity 27 32685100
2017 Tau-imaging in neurodegeneration. Methods (San Diego, Calif.) 27 28790016
2015 LRRK2 Facilitates tau Phosphorylation through Strong Interaction with tau and cdk5. Biochemistry 27 26268594
2023 The E3 Ubiquitin Ligase, CHIP/STUB1, Inhibits Aggregation of Phosphorylated Proteoforms of Microtubule-associated Protein Tau (MAPT). Journal of molecular biology 26 37330289
2019 Tau Modulates VGluT1 Expression. Journal of molecular biology 26 30664870
2023 Tau, tau kinases, and tauopathies: An updated overview. BioFactors (Oxford, England) 25 36688478
2021 Tau K321/K353 pseudoacetylation within KXGS motifs regulates tau-microtubule interactions and inhibits aggregation. Scientific reports 25 34426645
2020 Tau PET Imaging with [18F]PM-PBB3 in Frontotemporal Dementia with MAPT Mutation. Journal of Alzheimer's disease : JAD 25 32444551
2017 The evolution of interferon-tau. Reproduction (Cambridge, England) 25 28982935
2013 Potential synergy between tau aggregation inhibitors and tau chaperone modulators. Alzheimer's research & therapy 24 24041111