47 research outputs found

    Selective Molecular Alterations in the Autophagy Pathway in Patients with Lewy Body Disease and in Models of α-Synucleinopathy

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    Lewy body disease is a heterogeneous group of neurodegenerative disorders characterized by α-synuclein accumulation that includes dementia with Lewy bodies (DLB) and Parkinson's Disease (PD). Recent evidence suggests that impairment of lysosomal pathways (i.e. autophagy) involved in α-synuclein clearance might play an important role. For this reason, we sought to examine the expression levels of members of the autophagy pathway in brains of patients with DLB and Alzheimer's Disease (AD) and in α-synuclein transgenic mice.By immunoblot analysis, compared to controls and AD, in DLB cases levels of mTor were elevated and Atg7 were reduced. Levels of other components of the autophagy pathway such as Atg5, Atg10, Atg12 and Beclin-1 were not different in DLB compared to controls. In DLB brains, mTor was more abundant in neurons displaying α-synuclein accumulation. These neurons also showed abnormal expression of lysosomal markers such as LC3, and ultrastructural analysis revealed the presence of abundant and abnormal autophagosomes. Similar alterations were observed in the brains of α-synuclein transgenic mice. Intra-cerebral infusion of rapamycin, an inhibitor of mTor, or injection of a lentiviral vector expressing Atg7 resulted in reduced accumulation of α-synuclein in transgenic mice and amelioration of associated neurodegenerative alterations.This study supports the notion that defects in the autophagy pathway and more specifically in mTor and Atg7 are associated with neurodegeneration in DLB cases and α-synuclein transgenic models and supports the possibility that modulators of the autophagy pathway might have potential therapeutic effects

    Examining maladaptive beliefs about sleep across insomnia patient groups

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    Objectives Unhelpful beliefs about sleep have been linked to insomnia, and increasing one's cognitive flexibility about sleep has been linked to posttreatment sleep improvement. This study evaluated whether levels of such beliefs differ across insomnia groups and whether there are particular beliefs that differ for specific insomnia subtypes. Methods Participants (N=1384) were people with insomnia and good sleepers ranging from 18 to 89 years old (mean=42.6; S.D.=19.4). Data from previous studies at five insomnia clinical sites were pooled to examine responses on the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS) across differing insomnia groups. Results Group analyses revealed that those from community-based insomnia clinics and those who are hypnotic-dependent generally had the highest levels of unhelpful sleep-related beliefs. With the exception of beliefs about sleep needs (wherein only community sleep clinic patients had high scores relative to good sleepers), all insomnia groups had higher scores on the 16-item DBAS (DBAS-16) than good sleepers. A validity analysis suggested that a DBAS-16 index score of >3.8 represented the level of unhelpful beliefs associated with clinically significant insomnia, although a slightly lower cutoff may be useful for identifying an unhelpful degree of sleep-related beliefs in highly screened primary-insomnia-only and medical patient groups. Conclusions This study offers descriptive data for the use of DBAS-16 across insomnia subgroups, which will help the user understand what degree of maladaptive sleep beliefs is most strongly associated with clinically significant levels of insomnia. Results also may have implications for cognitive targeting during treatment for particular insomnia groups
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