Combinatorial PTM signatures distinguish pathological from physiological tau states

MAPT neurodegeneration market 54% active
Composite
46%
Novelty
50%
Feasibility
50%
Impact
—
Mechanistic
50%
Druggability
50%
Safety
50%
Confidence
50%

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.

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)

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%.