However, glucose metabolism dysregulation can also act upstream of the proteinopathies: genetic risk factors (such as C9), can modulate glucose metabolism in the absence of downstream proteinopathy, and a reduction of insulin signalling, can exacerbate Tauopathies, suggesting glucose metabolism dysregulation may act to exacerbate proteinopathy as well as downstream toxicity. This evidence concerns the gene INS and tauopathy.