The transmembrane amyloid precursor C99 protein exhibits non-specific interaction with tau.

ABSTRACT

Historically, the two most prominent proteins in Alzheimer's disease (AD) research have been the amyloid precursor protein (APP) and the microtubule assembly protein tau. In the classical model for the etiology of AD, amyloid-ß (Aß)-an APP derivative and hyperphosphorylated tau form aggregates in the brain that underlie the pathogenesis of the disease. However, the connection between Aß and tau pathologies remains unclear. Several studies have provided evidence that the presence of Aß can induce or enhance neurofibrillary tangle formation by tau. Others have reported a direct interaction between tau and short fragments of the APP transmembrane domain, C99. Structural studies of C99 show that these in vitro tau-binding fragments of C99 are buried in the lipid bilayer and are likely unavailable to bind tau in vivo. Given the importance of APP and tau in AD, we sought to characterize the potential interaction of the Aß precursor, full length C99, and tau in vitro using NMR spectroscopy. We found that C99 and soluble tau interact only weakly and, most likely, non-specifically.