# Tau isoform mapping across tissues and biofluids reveals a signature distinguishing Alzheimer's disease from amyotrophic lateral sclerosis

Article · Abu-Rumeileh S, Großkopf H, Guthknecht A, Mensch A, Osterloh D, Ratti A, Conrad J, Stapf C, Krippner J, Oeckl P, Stoltenburg-Didinger G, Maranzano A, Steinacker P, Weise CM, Barba L, D'Anna L, Klafki HW, Wiltfang J, Silani V, Froelich L, Ticozzi N, Hausner L, Thal DR, Weishaupt JH, Lachmann I and 2 more

- Archive id: doi:10.1038/s41467-026-78390-3
- Published: 2026-10-22
- Venue: Nature communications
- DOI: https://doi.org/10.1038/s41467-026-78390-3
- PMID: 42918778
- Citations: 0
- Source URL: https://doi.org/10.1038/s41467-026-78390-3
- Provenance: europepmc

## Abstract

Blood phosphorylated tau 217 (p-tau217) accurately detects Alzheimer's disease (AD) pathology but is also elevated in amyotrophic lateral sclerosis (ALS), likely reflecting peripheral (big) tau released from muscle. Assays selectively measuring brain-derived (BD-) tau and BD-p-tau217 are therefore needed. We analysed serum BD-tau and p-tau217 in ALS (n = 139), AD (n = 101) and controls (n = 75) using direct immunoassays and after BD-Tau immunoprecipitation (BD-Tau-IP), and tau species in brain (n = 16), spinal cord (n = 11) and muscle (n = 10) by targeted mass spectrometry. With the direct immunoassays, BD-tau and p-tau217 were increased in AD and ALS versus controls. After BD-Tau-IP, BD-tau and BD-p-tau217 were elevated in AD only, improving diagnostic accuracy. Mass spectrometry revealed a central-to-peripheral shift from BD-tau to big tau predominance, with exclusively big p-tau217 detected in muscle. Selective detection of BD-tau species improves the specificity of blood AD biomarkers by reducing peripheral tau confounding.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Alzheimer's, Parkinson's & Neurodegeneration](https://space-kitty.com/topics/neurodegeneration)

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