Axonal transport perturbations are known to play a critical role in the pathological progression of Alzheimers disease (AD); and Manganese-Enhanced MRI (MEMRI) provides a unique, non-invasive tool allowing for the in vivo evaluation of transport deficits in preclinical studies. In this paper, we provide a brief history of MEMRI, and review the current literature describing its biological basis. We propose a model of how manganese transport reflects both axonal and dendritic transport (termed “neuronal transport”), and potentially, mitochondrial trafficking in neurons. A framework for the analysis of MEMRI data is provided. It summarizes the significance of the various parameters describing manganese transport and the pathophysiological events that can alter their relevance, such as neuronal loss, gliosis and excitotoxicity. Lastly, we review publications describing different animal models of AD pathology that suggest the expression of either mutated human tau or mutated human amyloid β alters neuronal transport, as measured by MEMRI. In this way, MEMRI correlates the in vitro observation of impaired axonal transport and mitochondrial mislocalization related to AD lesions, with direct in vivo data. Therefore, MEMRI has the potential to become a unique tool for assessing the effect of new AD treatments aimed at restoring neuronal transport and mitochondrial trafficking.
Keywords: Alzheimer's disease, Amyloid β, animal models, axonal function, axonal transport, manganese, MEMRI, Tau, Amyloid Precursor Protein APP, Axons
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