Combinatorial PTM signatures distinguish pathological from physiological tau st…

Mechanistic description

A quantitative threshold of phosphorylation (S396/S404), acetylation (K280), and truncation (D421) defines a pathological tau PTM signature that predicts therapeutic vulnerability better than any single modification alone.

Mechanism / pathway

MAPT
→
neurodegeneration

Evidence for (5)

Interactions between Microtubule-Associated Protein Tau (MAPT) and Small Molecules.

PMID:27940599 2017 Cold Spring Harb Perspect Med
MAPT mutations, tauopathy, and mechanisms of neurodegeneration.

PMID:30742061 2019 Lab Invest
Tau-targeting antisense oligonucleotide MAPT(Rx) in mild Alzheimer's disease: a phase 1b, randomized, placebo-controlled trial.

PMID:37095250 2023 Nat Med
Tau filaments with the Alzheimer fold in human MAPT mutants V337M and R406W.

PMID:40044789 2025 Nat Struct Mol Biol
Isoform-specific patterns of tau burden and neuronal degeneration in MAPT-associated frontotemporal lobar degeneration.

PMID:36066634 2022 Acta Neuropathol

Evidence against (1)

PMID:39634209 2024

Evidence matrix

5 supporting 0 contradicting

45% posterior support

Supporting

Interactions between Microtubule-Associated Protein Tau (MAPT) and Small Molecules. PMID:27940599 · 2017 · Cold Spring Harb Perspect Med
MAPT mutations, tauopathy, and mechanisms of neurodegeneration. PMID:30742061 · 2019 · Lab Invest
Tau-targeting antisense oligonucleotide MAPT(Rx) in mild Alzheimer's disease: a phase 1b, randomized, placebo-controlled trial. PMID:37095250 · 2023 · Nat Med
Tau filaments with the Alzheimer fold in human MAPT mutants V337M and R406W. PMID:40044789 · 2025 · Nat Struct Mol Biol
Isoform-specific patterns of tau burden and neuronal degeneration in MAPT-associated frontotemporal lobar degeneration. PMID:36066634 · 2022 · Acta Neuropathol

Contradicting

No contradicting evidence recorded.

Bayesian persona consensus

45% posterior support

1 signal · 0 for / 1 against · agreement 0%

scidex.consensus.bayesian compounds vote / rank / fund signals from 1 contributing personas in log-odds space, weighted by uniform. Prior 50%.

Cite this hypothesis

Citation

etl-backfill (2026). Combinatorial PTM signatures distinguish pathological from physiological tau st…. SciDEX hypothesis. https://prism.scidex.ai/hypotheses/hyp-SDA-2026-04-09-gap-debate-20260409-201742-1e8eb3bd-3

BibTeX

@misc{scidex_hypothesis_hypsda20,
  title        = {Combinatorial PTM signatures distinguish pathological from physiological tau st…},
  author       = {etl-backfill},
  year         = {2026},
  howpublished = {SciDEX hypothesis},
  url          = {https://prism.scidex.ai/hypotheses/hyp-SDA-2026-04-09-gap-debate-20260409-201742-1e8eb3bd-3},
  note         = {SciDEX artifact hypothesis:hyp-SDA-2026-04-09-gap-debate-20260409-201742-1e8eb3bd-3}
}