4 documents found, page 1 of 1
Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72...
Wilson, Katherine M.; Katona, Eszter; Glaria, Idoia; Carcolé, Mireia; Swift, Imogen J.; Sogorb-Esteve, Aitana; Heller, Carolin; Bouzigues, ArabellaObjective: A GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. Our objective was to develop such an assay. Methods: We used the single molecule array (Sim...
Uncovering the heterogeneity and temporal complexity of neurodegenerative disea...
Young, Alexandra L.; Marinescu, Razvan V.; Oxtoby, Neil P.; Bocchetta, Martina; Yong, Keir; Firth, Nicholas C.; Cash, David M.; Thomas, David L.The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique-Subtype and Stage Inference (SuStaIn)-able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-se...
Analysis of shared heritability in common disorders of the brain
Anttila, Verneri; Bulik-Sullivan, Brendan; Finucane, Hilary K.; Walters, Raymond K.; Bras, Jose; Duncan, Laramie; Escott-Price, ValentinaDisorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common varian...
Genetic Variability in CLU and Its Association with Alzheimer's Disease
Guerreiro, Rita J.; Beck, John; Gibbs, J. Raphael; Santana, Isabel; Rossor, Martin N.; Schott, Jonathan M.; Nalls, Michael A.; Ribeiro, HelenaRecently, two large genome wide association studies in Alzheimer disease (AD) have identified variants in three different genes (CLU, PICALM and CR1) as being associated with the risk of developing AD. The strongest association was reported for an intronic single nucleotide polymorphism (SNP) in CLU. To further characterize this association we have sequenced the coding region of this gene in a total of 495 AD c...