11 documents found, page 1 of 2
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...
Polygenic transmission disequilibrium confirms that common and rare variation a...
Weiner, Daniel J.; Wigdor, Emilie M.; Ripke, Stephan; Walters, Raymond K.; Kosmicki, Jack A.; Grove, Jakob; Samocha, Kaitlin E.Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, ...
The choroid plexus transcriptome reveals changes in type I and II interferon re...
Mesquita, Sandro Gabriel Ferreira Dá; Ferreira, Ana C.; Gao, Fuying; Coppola, Giovanni; Geschwind, Daniel H.; Sousa, João CarlosAlzheimer's disease (AD) is a neurodegenerative disorder characterized by a marked decline in cognition and memory function. Increasing evidence highlights the essential role of neuroinflammatory and immune-related molecules, including those produced at the brain barriers, on brain immune surveillance, cellular dysfunction and amyloid beta (Aß) pathology in AD. Therefore, understanding the response at the brain...
Recurrent duplications of the annexin A1 gene (ANXA1) in autism spectrum disorders
Correia, Catarina T.; Conceição, Inês C.; Oliveira, Bárbara; Coelho, Joana; Sousa, Inês; Sequeira, Ana F.; Almeida, Joana; Café, Cátia; Duque, FredericoBackground: Validating the potential pathogenicity of copy number variants (CNVs) identified in genome-wide studies of autism spectrum disorders (ASD) requires detailed assessment of case/control frequencies, inheritance patterns, clinical correlations, and functional impact. Here, we characterize a small recurrent duplication in the annexin A1 (ANXA1) gene, identified by the Autism Genome Project (AGP) study. ...
Lipocalin 2 is present in the EAE brain and is modulated by natalizumab
Marques, Fernanda; Mesquita, Sandro; Sousa, João; Coppola, Giovanni; Gao, Fuying; Geschwind, Daniel H.; Columba-Cabezas, Sandra; Aloisi, FrancescaMultiple sclerosis (MS) is a demyelinating disease that causes major neurological disability in young adults. A definitive diagnosis at the time of the first episode is still lacking, but since early treatment leads to better prognosis, the search for early biomarkers is needed. Here we characterized the transcriptome of the choroid plexus (CP), which is part of the blood-brain barriers (BBBs) and the major sit...
Transcriptome signature of the adult mouse choroid plexus
Marques, Fernanda Cristina Gomes de Sousa; Sousa, João Carlos; Coppola, Giovanni; Gao, Fuying; Puga, Renato; Brentani, Helena; Geschwind, Daniel H.Background: Although the gene expression profile of several tissues in humans and in rodent animal models has been explored, analysis of the complete choroid plexus (CP) transcriptome is still lacking. A better characterization of the CP transcriptome can provide key insights into its functions as one of the barriers that separate the brain from the periphery and in the production of cerebrospinal fluid. Method...
Altered iron metabolism is part of the choroid plexus response to peripheral in...
Marques, Fernanda; Falcão, Ana M.; Sousa, João Carlos; Coppola, Giovanni; Geschwind, Daniel H.; Sousa, Nuno; Neves, Margarida CorreiaIron is essential for normal cellular homeostasis but in excess promotes free radical formation and is detrimental. Therefore, iron metabolism is tightly regulated. Here, we show that mechanisms regulating systemic iron metabolism may also control iron release into the brain at the blood-choroid plexus-cerebrospinal fluid (CSF) barrier. Intraperitoneal administration of lipopolysaccharide (LPS) in mice triggers...
Kinetic profile of the transcriptome changes induced in the choroid plexus by p...
Marques, Fernanda; Sousa, João Carlos; Coppola, Giovanni; Falcão, Ana Luisa Mendanha; Rodrigues, Ana João; Geschwind, Daniel H.; Sousa, NunoThe choroid plexus, being part of the blood-brain barriers and responsible for the production of cerebrospinal fluid, is ideally positioned to transmit signals into and out of the brain. This study, using microarray analysis, shows that the mouse choroid plexus displays an acute-phase response after an inflammatory stimulus induced in the periphery by lipopolysaccharide (LPS). Remarkably, the response is specif...
The choroid plexus response to a repeated peripheral inflammatory stimulus
Marques, Fernanda; Sousa, João Carlos; Coppola, Giovanni; Geschwind, Daniel H.; Sousa, Nuno; Palha, Joana Almeida; Neves, Margarida CorreiaBACKGROUND: Chronic systemic inflammation triggers alterations in the central nervous system that may relate to the underlying inflammatory component reported in neurodegenerative disorders such as multiple sclerosis and Alzheimer's disease. However, it is far from being understood whether and how peripheral inflammation contributes to induce brain inflammatory response in such illnesses. As part of the barrier...
Lipocalin 2 is a choroid plexus acute-phase protein
Marques, Fernanda; Rodrigues, Ana João; Sousa, João Carlos; Coppola, Giovanni; Geschwind, Daniel H.; Sousa, Nuno; Correia-Neves, M; Palha, Joana AlmeidaLipocalin 2 (LCN2) is able to sequester iron-loaded bacterial siderophores and, therefore, is known to participate in the mammalian innate immune response. Of notice, LCN2 was shown to display bacteriostatic effects both in in vitro and in vivo. To reach the brain, bacteria must cross the blood-brain or the choroid plexus (CP)/cerebrospinal fluid (CSF) barriers. Additionally, as the CP is responsible for the pr...