The Collagen Chaperone HSP47 Is a New Interactor of APP that Affects the Levels of Extracellular Beta-Amyloid Peptides

Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive decline of cognitive function that represents one of the most dramatic medical challenges for the aging population. Aβ peptides, generated by processing of the Amyloid Precursor Protein (APP), are thought to play a central role in the pathogenesis of AD. However, the network of physical and functional interactions that may affect their production and deposition is still poorly understood. The use of a bioinformatic approach based on human/mouse conserved coexpression allowed us to identify a group of genes that display an expression profile strongly correlated with APP. Among the most prominent candidates, we investigated whether the collagen chaperone HSP47 could be functionally correlated with APP. We found that HSP47 accumulates in amyloid deposits of two different mouse models and of some AD patients, is capable to physically interact with APP and can be relocalized by APP overexpression. Notably, we found that it is possible to reduce the levels of secreted Aβ peptides by reducing the expression of HSP47 or by interfering with its activity via chemical inhibitors. Our data unveil HSP47 as a new functional interactor of APP and imply it as a potential target for preventing the formation and/or growth amyloid plaques

Empathic abilities in people with schizophrenia

PubMed ID: 18514324Although the existence of empathy deficits in schizophrenia is generally accepted, very few studies have directly investigated the issue. The nature of empathy deficits in healthy subjects and psychiatric patients is an understudied subject. The performances of the 30 outpatients with schizophrenia on a psychometric measure, the Empathy Quotient (EQ), were compared with those of 30 control subjects matched for age, duration of education and gender. The relatives or spouses of the patients also filled out the EQ. A neuropsychological battery, including emotion recognition, emotional reasoning and theory of mind tasks, was also administered. Schizophrenia patients had severe empathy dysfunction based on their relative EQ ratings. There was a serious discrepancy between the self and relative/spouse assessments of the empathic skills of schizophrenia patients. Consistent with the previous findings schizophrenia patients were impaired in nearly all cognitive tasks. The empathy deficits of schizophrenia patients were associated with their impairments in other social cognitive tasks. Studies focusing on dysfunctional brain networks underlying empathy deficits and studies using more experimental measures of empathy should be helpful to unravel the true nature of the empathic failure in patients with schizophrenia. © 2007 Elsevier Ireland Ltd. All rights reserved.John D. and Catherine T. MacArthur FoundationDevelopment of the MacBrain Face Stimulus Set was overseen by Nim Tottenham and supported by the John D. and Catherine T. MacArthur Foundation Research Network on Early Experience and Brain Development. Please contact Nim Tottenham at [email protected] for more information concerning the stimulus set. -

The effect of galantamine added to clozapine on cognition of five patients with schizophrenia

WOS: 000230220600009PubMed ID: 15965314Although clozapine may be beneficial for the treatment of cognitive dysfunction in schizophrenia, it may also impair some cognitive skills as a result of its anticholinergic activity. In this case series, the impact of galantamine administration on 5 patients with schizophrenia who had been treated with clozapine are reported. Neuropsychological assessment was administered before and after 8 weeks of 16 mg/d galantamine treatment. In this case series, galantamine was well tolerated by all of the patients. Three of the patients were much improved in sustained attention tasks. Most of the patients were also improved in psychomotor speed and selective attention tasks. Two patients with low pretreatment memory scores seemed to also be improved. Our results suggest that the possible role of galantamine as a cognitive enhancer in schizophrenia should be investigated in controlled trials

Theory of mind and executive functioning in bipolar disorder and schizophrenia

9th International Conference on Bipolar Disorder -- JUN 09-11, 2011 -- Pittsburgh, PAWOS: 00030010240005

Theory of mind and unawareness of illness in schizophrenia: Is poor insight a mentalizing deficit?

PubMed ID: 17171312This study investigates the impact of theory of mind (ToM) deficits on poor insight in schizophrenia. The scale for unawareness of mental disorder (SUMD) was administered to 58 stable outpatients with schizophrenia. First and second order false belief tasks, the Eyes test and a battery of nonToM cognitive measures were administered. The Second order false belief task was the best predictor of each global insight and symptom attribution scores of the SUMD. ToM tasks explained the substantial amount of the variance (ranging from 22.5% to 29.9%) for the insight scores and classified the significant amount of the patients who were aware of the illness correctly. WCST perseveration scores did not contribute to insight scores beyond that contributed by second order false belief tasks. The Second order ToM tasks seems to have critical importance for the awareness of the disorder. Beyond more direct self-evaluation, the awareness of the disorder and its consequences may also require the ability to evaluate the self from the perspective of others. "Understanding the others' belief about another person" may be conceptually very similar to "understanding the others' belief about self" (instead of another person). © 2006 Steinkopff Verlag