The Mechanism for Tau Tangles (LB102)

Alzheimer’s disease (AD) affects more than 5.2 million people in the US. The disease is characterized by the presence of “Tau Tangles”, which is the aggregation of the protein Tau. The Tau protein is expressed in the nervous system and helps stabilize microtubules, which help establish cell shape and serve as tracks for neuronal transport. The Tau protein is regulated through phosphorylation and in patients with AD, the Tau protein is hyperphosphorylated, which can lead to the formation of “Tau Tangles”. These tangles are made up of free floating Tau and can interfere in the neuron communication because of a structural change in the protein due to the phosphorylation. In a normal mature neuron, tubulin is present in over tenfold excess of the Tau protein, and almost all Tau protein is bound to microtubules. In AD, the ratio between free floating Tau and microtubule bound Tau increases. In neurons affected by AD, hyperphosphorylated and glycosylated Tau disengages from microtubules and disrupts microtubule organization. Tau kinases phosphorylate Tau; however the regulation of Tau phosphorylation is still unknown. The Olathe North SMART Team (Students Modeling A Research Topic) modeled the Tau kinase using 3D printing technology . Grant Funding Source : Supported by grants from the NIH‐SEPA and NIH‐CTSA.