15 documents found, page 1 of 2
Altered plasma protein profiles in genetic FTD – a GENFI study
Ullgren, Abbe; Öijerstedt, Linn; Olofsson, Jennie; Bergström, Sofia; Remnestål, Julia; van Swieten, John C.; Jiskoot, Lize C.; Seelaar, HarroBackground: Plasma biomarkers reflecting the pathology of frontotemporal dementia would add significant value to clinical practice, to the design and implementation of treatment trials as well as our understanding of disease mechanisms. The aim of this study was to explore the levels of multiple plasma proteins in individuals from families with genetic frontotemporal dementia. Methods: Blood samples from 693 pa...
A data-driven disease progression model of fluid biomarkers in genetic frontote...
van der Ende, Emma L.; Bron, Esther E.; Poos, Jackie M.; Jiskoot, Lize C.; Panman, Jessica L.; Papma, Janne M.; Meeter, Lieke H.; Dopper, Elise G. P.Several CSF and blood biomarkers for genetic frontotemporal dementia have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain and phosphorylated neurofilament heavy chain), synapse dysfunction [neuronal pentraxin 2 (NPTX2)], astrogliosis (glial fibrillary acidic protein) and complement activation (C1q, C3b). Determining the sequence in which biomarkers become abnormal over the ...
Elevated CSF and plasma complement proteins in genetic frontotemporal dementia:...
van der Ende, Emma L.; Heller, Carolin; Sogorb-Esteve, Aitana; Swift, Imogen J.; McFall, David; Peakman, Georgia; Bouzigues, Arabella; Poos, Jackie M.Background: Neuroinflammation is emerging as an important pathological process in frontotemporal dementia (FTD), but biomarkers are lacking. We aimed to determine the value of complement proteins, which are key components of innate immunity, as biomarkers in cerebrospinal fluid (CSF) and plasma of presymptomatic and symptomatic genetic FTD mutation carriers. Methods: We measured the complement proteins C1q and ...
Common variants in Alzheimer's disease and risk stratification by polygenic ris...
de Rojas, Itziar; Moreno-Grau, Sonia; Tesi, Niccolo; Grenier-Boley, Benjamin; Andrade, Victor; Jansen, Iris E.; Pedersen, Nancy L.; Stringa, NajadaGenetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Her...
Stratifying the presymptomatic phase of genetic frontotemporal dementia by Seru...
Wilke, Carlo; Reich, Selina; Swieten, John C.; Borroni, Barbara; Sanchez‐Valle, Raquel; Moreno, Fermin; Laforce, Robert; Graff, CarolineObjective: Although the presymptomatic stages of frontotemporal dementia (FTD) provide a unique chance to delay or even prevent neurodegeneration by early intervention, they remain poorly defined. Leveraging a large multicenter cohort of genetic FTD mutation carriers, we provide a biomarker-based stratification and biomarker cascade of the likely most treatment-relevant stage within the presymptomatic phase: th...
Age at symptom onset and death and disease duration in genetic frontotemporal d...
Moore, Katrina M.; Nicholas, Jennifer; Grossman, Murray; McMillan, Corey T.; Irwin, David J.; Massimo, Lauren; Van Deerlin, Vivianna M.Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT,...
Brain functional network integrity sustains cognitive function despite atrophy ...
Tsvetanov, Kamen A.; Gazzina, Stefano; Jones, P. Simon; Swieten, John; Borroni, Barbara; Sanchez‐Valle, Raquel; Moreno, Fermin; Laforce, RobertIntroduction: The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial frontotemporal dementia (FTD). Methods: We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both struc...
Functional network resilience to pathology in presymptomatic genetic frontotemp...
Rittman, Timothy; Borchert, Robin; Jones, Simon; van Swieten, John; Borroni, Barbara; Galimberti, Daniela; Masellis, Mario; Tartaglia, Maria CarmelaThe presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied 172 people from families carrying genetic abnormalities in C9orf72, MAPT, or PGRN. Networks were extracted from f...
The inner fluctuations of the brain in presymptomatic frontotemporal dementia: ...
Premi, Enrico; Calhoun, Vince D.; Diano, Matteo; Gazzina, Stefano; Cosseddu, Maura; Alberici, Antonella; Archetti, Silvana; Paternicò, DonataFrontotemporal Dementia (FTD) is preceded by a long period of subtle brain changes, occurring in the absence of overt cognitive symptoms, that need to be still fully characterized. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) is a potentially powerful tool for the study of preclinical FTD. In the present study, we employed a "chronnectome" approach (recurring, time-varyin...
Clinical value of cerebrospinal fluid neurofilament light chain in semantic dem...
Meeter, Lieke H. H.; Steketee, Rebecca M. E.; Salkovic, Dina; Vos, Maartje E.; Grossman, Murray; McMillan, Corey T.; Irwin, David J.; Boxer, Adam L.Background: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FT...