Anti-NEFH (aa 263-363) polyclonal antibody

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease and the proteins and pathways involved in the pathophysiology are not fully understood. Even less is known about the preclinical disease phase. To uncover new ALS-related proteins and pathways, we performed a comparative proteomic analysis in cerebrospinal fluid (CSF) of asymptomatic (n = 14) and symptomatic (n = 14) ALS mutation carriers and sporadic ALS patients (n = 12) as well as post-mortem human spinal cord tissue (controls: n = 7, ALS, n = 8). Using a CSF-optimized proteomic workflow, we identified novel (e.g., UCHL1, MAP2, CAPG, GPNMB, HIST1H4A, HIST1H2B) and well-described (e.g., NEFL, NEFH, NEFM, CHIT1, CHI3L1) protein level changes in CSF of sporadic and genetic ALS patients with enrichment of proteins related to transcription, cell cycle and lipoprotein remodeling (total protein IDs: 2303). No significant alteration was observed in asymptomatic ALS mutation carriers representing the prodromal disease phase. We confirmed UCHL1, MAP2, CAPG and GPNMB as novel biomarker candidates for ALS in an independent validation cohort of patients (n = 117) using multiple reaction monitoring. In spinal cord tissue, 292 out of 6810 identified proteins were significantly changed in ALS with enrichment of proteins involved in mRNA splicing and of the neurofilament compartment. In conclusion, our proteomic data in asymptomatic ALS mutation carriers support the hypothesis of a sudden disease onset instead of a long preclinical phase. Both CSF and tissue proteomic data indicate transcriptional pathways to be amongst the most affected. UCHL1, MAP2 and GPNMB are promising ALS biomarker candidates which might provide additional value to the established neurofilaments in patient follow-up and clinical trials.

Purpose of review Clinical outcome after neurotrauma is considerably variable and can only partly be explained by known prognostic factors. There is converging evidence from genetic research that a number of genetic variants may contribute to this variability. This review provides recent data from human studies, published in the previous year, on genetic factors influencing outcome after neurotrauma. The bibliographic databases MEDLINE, EMBASE and PsycINFO were searched to identify relevant studies. Recent findings Genetic susceptibility to various aspects of clinical outcome after neurotrauma was reported in recent clinical studies. Genetic loci investigated include polymorphisms in APOE, MAO-A, BDNF, NOS3, IL-6, NEFH, SLC6A4, COMT, PPP3CC and KIBRA genes. The importance of these findings and future directions are discussed. Summary Recent genetic studies have revealed emerging aspects and extended the existing knowledge regarding the pathogenesis of neurotrauma and the genetic influence on phenotypic diversity. A better understanding of the underlying biological pathways and molecular mechanisms of an individual's response to neurotrauma may hold the promise of novel treatment strategies and improved clinical outcome.