Tau isoform mapping across tissues and biofluids reveals a signature distinguishing Alzheimer’s disease from amyotrophic lateral sclerosis
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.
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BibTeX
@article{aburumeileh2026isoform,
title = {{Tau isoform mapping across tissues and biofluids reveals a signature distinguishing Alzheimer’s disease from amyotrophic lateral sclerosis}},
author = {Samir Abu-Rumeileh and Henning Großkopf and Arthur Guthknecht and Alexander Mensch and Dirk Osterloh and Antonia Ratti and Julian Conrad and Caroline Stapf and Julia Krippner and Patrick Oeckl and Gisela Stoltenburg-Didinger and Alessio Maranzano and Petra Steinacker and Christopher M. Weise and Lorenzo Barba and Lucio D’Anna and Hans-Wolfgang Klafki and Jens Wiltfang and Vincenzo Silani and Lutz Froelich and Nicola Ticozzi and Lucrezia Hausner and Dietmar Rudolf Thal and Jochen Hans Weishaupt and Ingolf Lachmann and Federico Verde and Markus Otto},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78390-3},
url = {https://www.nature.com/articles/s41467-026-78390-3},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tau isoform mapping across tissues and biofluids reveals a signature distinguishing Alzheimer’s disease from amyotrophic lateral sclerosis
AU - Samir Abu-Rumeileh
AU - Henning Großkopf
AU - Arthur Guthknecht
AU - Alexander Mensch
AU - Dirk Osterloh
AU - Antonia Ratti
AU - Julian Conrad
AU - Caroline Stapf
AU - Julia Krippner
AU - Patrick Oeckl
AU - Gisela Stoltenburg-Didinger
AU - Alessio Maranzano
AU - Petra Steinacker
AU - Christopher M. Weise
AU - Lorenzo Barba
AU - Lucio D’Anna
AU - Hans-Wolfgang Klafki
AU - Jens Wiltfang
AU - Vincenzo Silani
AU - Lutz Froelich
AU - Nicola Ticozzi
AU - Lucrezia Hausner
AU - Dietmar Rudolf Thal
AU - Jochen Hans Weishaupt
AU - Ingolf Lachmann
AU - Federico Verde
AU - Markus Otto
PY - 2026
DA - 2026/10/22
JO - Nature Communications
DO - 10.1038/s41467-026-78390-3
UR - https://www.nature.com/articles/s41467-026-78390-3
AB - 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.
SN - 2041-1723
ER -