Tau isoform mapping across tissues and biofluids reveals a signature distinguishing Alzheimer’s disease from amyotrophic lateral sclerosis
Year: 2026
Type: article
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.
Source: Nature Communications
Authors: Samir Abu-Rumeileh, Henning Großkopf, Arthur Guthknecht, Alexander Mensch, Dirk Osterloh, Antonia Ratti, Julian Conrad, Caroline Stapf, Julia Krippner, Patrick Oeckl, Gisela Stoltenburg-Didinger, Alessio Maranzano, Petra Steinacker, Christopher M. Weise, Lorenzo Barba, Lucio D’Anna, Hans-Wolfgang Klafki, Jens Wiltfang, Vincenzo Silani, Lutz Froelich, Nicola Ticozzi, Lucrezia Hausner, Dietmar Rudolf Thal, Jochen Hans Weishaupt, Ingolf Lachmann, Federico Verde, Markus Otto
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7223176302