87 research outputs found

    Imaging noradrenergic influence on amyloid pathology in mouse models of Alzheimer’s disease

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    peer reviewedMolecular imaging aims towards the non-invasive characterization of disease-specific molecular alterations in the living organism in vivo. In that, molecular imaging opens a new dimension in our understanding of disease pathogenesis, as it allows the non-invasive determination of the dynamics of changes on the molecular level. IMAGING OF AD CHARACTERISTIC CHANGES BY microPET: The imaging technology being employed includes magnetic resonance imaging (MRI) and nuclear imaging as well as optical-based imaging technologies. These imaging modalities are employed together or alone for disease phenotyping, development of imaging-guided therapeutic strategies and in basic and translational research. In this study, we review recent investigations employing positron emission tomography and MRI for phenotyping mouse models of Alzheimer's disease by imaging. We demonstrate that imaging has an important role in the characterization of mouse models of neurodegenerative diseases

    Immunomodulation Targeting Abnormal Protein Conformation Reduces Pathology in a Mouse Model of Alzheimer's Disease

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    Many neurodegenerative diseases are characterized by the conformational change of normal self-proteins into amyloidogenic, pathological conformers, which share structural properties such as high ÎČ-sheet content and resistance to degradation. The most common is Alzheimer's disease (AD) where the normal soluble amyloid ÎČ (sAÎČ) peptide is converted into highly toxic oligomeric AÎČ and fibrillar AÎČ that deposits as neuritic plaques and congophilic angiopathy. Currently, there is no highly effective treatment for AD, but immunotherapy is emerging as a potential disease modifying intervention. A major problem with most active and passive immunization approaches for AD is that both the normal sAÎČ and pathogenic forms are equally targeted with the potential of autoimmune inflammation. In order to avoid this pitfall, we have developed a novel immunomodulatory method that specifically targets the pathological conformations, by immunizing with polymerized British amyloidosis (pABri) related peptide which has no sequence homology to AÎČ or other human proteins. We show that the pABri peptide through conformational mimicry induces a humoral immune response not only to the toxic AÎČ in APP/PS1 AD transgenic mice but also to paired helical filaments as shown on AD human tissue samples. Treated APP/PS1 mice had a cognitive benefit compared to controls (p<0.0001), associated with a reduction in the amyloid burden (p = 0.0001) and AÎČ40/42 levels, as well as reduced AÎČ oligomer levels. This type of immunomodulation has the potential to be a universal ÎČ-sheet disrupter, which could be useful for the prevention or treatment of a wide range of neurodegenerative diseases

    Crosstalk Between Macroautophagy and Chaperone-Mediated Autophagy: Implications for the Treatment of Neurological Diseases

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    International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

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    Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

    Hemispheric processing of Chinese hĂ nzĂŹ and English words: A lateralized lexical decision study

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    Abstract: We presented orthographic English words or Chinese logographic hĂ nzĂŹ primes to either the left or right visual fields followed by a semantically related target to the opposite visual field. Chinese hĂ nzĂŹ primed English words in both hemispheres but English required right-hemisphere involvement to prime hĂ nzĂŹ symbols. This study suggests that Chinese hĂ nzĂŹ and English word translation recruits both hemispheres. Our results are consistent with the conclusion that the two cortical hemispheres maintain parallel, but different, representations of hĂ nzĂŹ, just as has been shown with English words
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