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    Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of Alzheimer's Disease

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    Author
    Portbury, SD; Hare, DJ; Sgambelloni, C; Perronnes, K; Portbury, AJ; Finkelstein, DI; Adlard, PA
    Date
    2017-01-01
    Source Title
    Journal of Alzheimer's Disease
    Publisher
    IOS PRESS
    University of Melbourne Author/s
    Finkelstein, David; Portbury, Stuart; Adlard, Paul; Hare, Dominic
    Affiliation
    Florey Department of Neuroscience and Mental Health
    School of BioSciences
    Metadata
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    Document Type
    Journal Article
    Citations
    Portbury, S. D., Hare, D. J., Sgambelloni, C., Perronnes, K., Portbury, A. J., Finkelstein, D. I. & Adlard, P. A. (2017). Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of Alzheimer's Disease. JOURNAL OF ALZHEIMERS DISEASE, 60 (2), pp.549-560. https://doi.org/10.3233/JAD-170322.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256837
    DOI
    10.3233/JAD-170322
    Abstract
    This study assessed the therapeutic utility of the autophagy enhancing stable disaccharide trehalose in the Tg2576 transgenic mouse model of Alzheimer's disease (AD) via an oral gavage of a 2% trehalose solution for 31 days. Furthermore, as AD is a neurodegenerative condition in which the transition metals, iron, copper, and zinc, are understood to be intricately involved in the cellular cascades leading to the defining pathologies of the disease, we sought to determine any parallel impact of trehalose treatment on metal levels. Trehalose treatment significantly improved performance in the Morris water maze, consistent with enhanced learning and memory. The improvement was not associated with significant modulation of full length amyloid-β protein precursor or other amyloid-β fragments. Trehalose had no effect on autophagy as assessed by western blot of the LC3-1 to LC3-2 protein ratio, and no alteration in biometals that might account for the improved cognition was observed. Biochemical analysis revealed a significant increase in the hippocampus of both synaptophysin, a synaptic vesicle protein and surrogate marker of synapses, and doublecortin, a reliable marker of neurogenesis. The growth factor progranulin was also significantly increased in the hippocampus and cortex with trehalose treatment. This study suggests that trehalose might invoke a suite of neuroprotective mechanisms that can contribute to improved cognitive performance in AD that are independent of more classical trehalose-mediated pathways, such as Aβ reduction and activation of autophagy. Thus, trehalose may have utility as a potential AD therapeutic, with conceivable implications for the treatment of other neurodegenerative disorders.

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