Phosphorylated tau 181 and 217 are elevated in serum and muscle of patients with amyotrophic lateral sclerosis
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.
Authors
- Anne Kölsch
- Samir Abu‐Rumeileh (ORCID: https://orcid.org/0000-0003-0631-8506)
- Julian Conrad (ORCID: https://orcid.org/0000-0001-7912-0571)
- Leila Motlagh Scholle (ORCID: https://orcid.org/0000-0003-1363-4726)
- Steffen Halbgebauer (ORCID: https://orcid.org/0000-0002-8711-5702)
- Antonia Ratti (ORCID: https://orcid.org/0000-0002-4264-6614)
- Vincenzo Silani (ORCID: https://orcid.org/0000-0002-7698-3854)
- Alexander Mensch (ORCID: https://orcid.org/0000-0003-0089-4473)
- Henning Großkopf (ORCID: https://orcid.org/0000-0002-5122-2477)
- Caroline Stapf
- Andreas Posa (ORCID: https://orcid.org/0000-0001-9807-6780)
- Lucrezia Hausner (ORCID: https://orcid.org/0000-0001-9009-2356)
- Nicola Ticozzi (ORCID: https://orcid.org/0000-0001-5963-7426)
- Gisela Stoltenburg‐Didinger (ORCID: https://orcid.org/0000-0002-2534-3064)
- Patrick Oeckl (ORCID: https://orcid.org/0000-0002-7652-7023)
- Lutz Froelich (ORCID: https://orcid.org/0000-0003-1494-0813)
- Lorenzo Barba (ORCID: https://orcid.org/0000-0003-1328-3620)
- Hans‐Wolfgang Klafki (ORCID: https://orcid.org/0000-0002-8672-9032)
- Jochen Hans Weishaupt (ORCID: https://orcid.org/0000-0002-3399-9784)
- Federico Verde (ORCID: https://orcid.org/0000-0002-3977-6995)
- Thomas Kendzierski
- Markus Otto (ORCID: https://orcid.org/0000-0003-4273-4267)
- Petra Steinacker
- Anna De Gobbi
Institutions
- University of Milan (IT)
- Heidelberg University (DE)
- German Center for Neurodegenerative Diseases (DE)
- University Hospital Heidelberg (DE)
- Central Institute of Mental Health (DE)
- IRCCS Istituto Auxologico Italiano (IT)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- University Hospital Ulm (DE)
- Ferrari (Italy) (IT)
- Martin Luther University Halle-Wittenberg (DE)
- University of Göttingen (DE)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-05
- DOI
- https://doi.org/10.1038/s41467-025-57144-7
- Citations
- 43
- Primary Topic
- Amyotrophic Lateral Sclerosis Research
- Type
- article
- Field-Weighted Citation Impact
- 59.74