Phosphorylated tau 181 and 217 are elevated in serum and muscle of patients with amyotrophic lateral sclerosis
Samir Abu‐Rumeileh, Leila Motlagh Scholle, Alexander Mensch, Henning Großkopf, Antonia Ratti, Anne Kölsch, Gisela Stoltenburg‐Didinger, Julian Conrad, Anna De Gobbi, Lorenzo Barba, Petra Steinacker, Hans‐Wolfgang Klafki, Patrick Oeckl, Steffen Halbgebauer, Caroline Stapf, Andreas Posa, Thomas Kendzierski, Vincenzo Silani, Lucrezia Hausner, Nicola Ticozzi, Lutz Froelich, Jochen H. Weishaupt, Federico Verde, Markus Otto
Abstract
Blood phosphorylated (p)-tau 181 and p-tau 217 have been proposed as accurate biomarkers of Alzheimer's disease (AD) pathology. However, blood p-tau 181 is also elevated in amyotrophic lateral sclerosis (ALS) without a clearly identified source. We measured serum p-tau 181 and p-tau 217 in a multicentre cohort of ALS (n = 152), AD (n = 111) cases and disease controls (n = 99) recruited from four different centres. Further, we investigated the existence of both p-tau species using immunohistochemistry (IHC) and mass spectrometry (MS) in muscle biopsies of ALS cases (IHC: n = 13, MS: n = 5) and disease controls (IHC: n = 14, MS: n = 5) from one cohort. Serum p-tau 181 and p-tau 217 were higher in AD and ALS patients compared to disease controls. IHC and MS analyses revealed the presence of p-tau 181 and 217 in muscle biopsies from both ALS cases and disease controls, with ALS samples showing increased p-tau reactivity in atrophic muscle fibres. Blood p-tau species could potentially be used to diagnose both ALS and AD.