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Defining the pathogenic relationship of TDP-43 inclusions and cytoplasmic double stranded RNA in AD and FTD

US National Institute on Aging grant open #nih-4R01AG078377-02

Summary

Abstract Cytoplasmic inclusions of TDP-43 (TAR DNA-binding protein 43) are found in many patients with Alzheimer's disease (AD). The presence of TDP-43 inclusions predicts a steeper cognitive decline after controlling for other pathologies. TDP-43 cytoplasmic inclusions are also present in > 45% of cases of frontotemporal dementia (FTD), including all cases associated with C9ORF72 repeat expansion, which is the most common genetic mutation causing of FTD. Cytoplasmic aggregates of TDP-43 are hypothesized to sequester the protein from physiological targets, thereby mimicking loss of function mu

Defining the pathogenic relationship of TD…
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