Catalytic Prion-like Cross-talk between a key Alzheimer’s disease Tau-fragment R3 and the Type 2 Diabetes peptide IAPP

The aberrant association of proteins/peptides is implicated in the etiology and pathogenesis of a variety of human diseases. In general, the primary protein component responsible for the formation of aggregates is different in each case and is specific to a particular disease condition. However, there are instances where multiple protein aggregates have been found to co-exist in the same or different tissue(s), thereby leading to mixed pathologies and exacerbation of disease symptoms. In this context, a strong link has been established between Alzheimer’s disease (AD) and Type 2 Diabetes (T2D). However, the underlying molecular details still remain elusive. Here, we report the direct interaction of an AD associated amyloidogenic cytotoxic fragment of Tau (R3: 306-336) with islet amyloid polypeptide (IAPP) implicated in T2D. Using ion-mobility mass spectrometry (IM-MS) in conjunction with fluorescence spectroscopy, circular dichroism and transmission electron microscopy, we have been able to provide critic...