Apolipoprotein E and Tau interaction in Alzheimer's disease.

Tau, an intrinsically disordered protein associated with microtubule stabilization, is crucial for cellular trafficking, and signaling pathways. Under pathological conditions, Tau undergoes post-translational modifications and structural changes, leading to its aggregation into neurofibrillary tangles (NFTs). The interactions between Tau and membrane lipids, including phospholipids like DOPC, DPPC, and proteins such as Apo E4, play a significant role in Tau aggregation. These interactions modulate Tau's structure, stabilization, and aggregation kinetics. Phospholipase C (PLC) and DEPC also influence Tau aggregation through signaling pathways and preservation of RNA integrity, respectively. Membrane lipid composition affects Tau-membrane interactions, which can promote Tau fibrillization and propagation, contributing to neurotoxicity in Alzheimer's disease (AD) and other Tauopathies. The disruption of lipid homeostasis by Apo E4, alterations in membrane fluidity and integrity by DPPC, and the influence of phospholipids on BBB functionality are significant in understanding Tau pathology.