Tau and Lipid Dysregulation in Alzheimer's Disease

Voiceover

Presenter(s)

Amanda Hertel

Abstract or Description

This research explores how tau protein and lipid membranes interact through protein aggregation and membrane disruption as a potential contributor to Alzheimer's Disease (AD) progression. Wild-type tau protein serves important roles in microtubule stability and binding in neurons. However, when tau accumulates, it can become neurotoxic, leading to tauopathies, a class of neurodegenerative disorders characterized by tau aggregation, like AD. Due to abnormal interactions, tau protein can exist in various phosphorylated states. This phosphorylation is thought to be a leading factor in oligomer (small protein polymers) and neurofibrillary tangle (NFT) formation. While it's known that tau, lipids, and phosphorylation play a role in AD progression, details of the specific mechanism are still unclear. This work aims to progress the field by studying various mechanical and film properties of tau and lipids using Langmuir Troughs. A Langmuir trough has a moveable barrier that measures the surface properties of lipid membranes at air/liquid interfaces. The liquid phase is a HEPES + DTT buffer, resembling physiological conditions. Lipids modeling central nervous system (CNS) neurons are spread onto the buffer, forming a monolayer, and protein is injected. Various pseudophosphorylated tau mutants were compared to wild-type tau protein (htau40). Both isotherm and adsorption studies were performed to study the mechanical film properties and adsorption kinetics. Based on the results, the addition of phosphorylated tau was found to lower mechanical properties, suggesting that it disrupts lipid packing. By studying these tau-lipid interactions, we aim to better identify this potential mechanism contributing to AD.

Mentor

Prajnaparamita Dhar