ABSTRACT Background Seed amplification assays (SAA) detect alpha‐synuclein (aSYN) pathology in patient biomatrices such as cerebrospinal fluid (CSF)—potentially even before clinical manifestations. As CSF‐based SAA are approaching broader use in clinical trials and research, ensuring that different laboratories obtain the same results becomes increasingly important. Methods In this cross‐laboratory, cross‐aSYN‐recombinant substrate and cross‐protocol round‐robin test, we compared SAA results from a common set of 3…

ABSTRACT Background Over the past years, some studies in amyotrophic lateral sclerosis (ALS) have provided heterogeneous findings regarding demographic and clinical data as well as the impact of various prognostic factors. It is well known that these inconsistencies might be caused by a selection bias in hospital‐based data sets. In this study, we sought to further characterize this selection bias. Methods We compared hospital‐based data from the ALS center at Ulm University (UC; n = 3833; 1997–2021) with the popu…

Objective Tofersen is the first effective and approved therapy for superoxide dismutase 1 ( SOD1 )‐associated amyotrophic lateral sclerosis (ALS [SOD1‐ALS]). Following treatment with tofersen, neurofilament levels in patients' cerebrospinal fluid (CSF) and serum seem to respond earlier than clinical parameters. This evidence prompted us to hypothesize that this novel treatment could provide an opportunity to identify additional biomarkers responsive to therapy in SOD1‐ALS. Methods We investigated a panel of 120 ne…

Objective Neurofilament light chains (NfL) and phosphorylated neurofilament heavy chains (pNfH), established as diagnostic and prognostic biomarkers in hospital‐based amyotrophic lateral sclerosis (ALS) cohorts, are now surrogate markers in clinical trials. This study extends their evaluation to a population level, with the aim of advancing their full establishment and assessing the transferability of biomarker findings from controlled cohorts to real‐world ALS populations. Methods We measured serum NfL and pNfH l…

Heterozygous mutations in the TBK1 gene can cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The majority of TBK1-ALS/FTD patients carry deleterious loss-of-expression mutations, and it is still unclear which TBK1 function leads to neurodegeneration. We investigated the impact of the pathogenic TBK1 missense variant p.E696K, which does not abolish protein expression, but leads to a selective loss of TBK1 binding to the autophagy adaptor protein and TBK1 substrate optineurin. Using organ…