Tip-enhanced Raman spectroscopy reveals the structural rearrangements of tau protein aggregates at the growth phase

Tau protein aggregates inside neurons in the course of Alzheimer's disease (AD). Because of the enormous number of people suffering from AD, this disease has become one of the world's major health and social problems. The presence of tau lesions clearly correlates with cognitive impairments in AD patients, thus, tau is the target of potential treatments for AD, next to amyloid-β. The exact mechanism of tau aggregation has not been understood in detail so far; especially little is known about the structural rearrangements of tau aggregates at the growth phase. The research into tau conformation at each step of the aggregation pathway will contribute to the design of effective therapeutic approaches. To follow the secondary structure of individual tau aggregates at the growth phase, we applied tip-enhanced Raman spectroscopy (TERS). The nanospectroscopic approach enabled us to follow the structure of individual aggregates occurring in the subsequent phases of tau aggregation. We applied multivariate data analysis to extract the spectral differences for tau aggregates at different aggregation phases. Moreover, atomic force microscopy (AFM) allowed the tracking of the morphological alterations for species occurring with the progression of tau aggregation. Tip-enhanced Raman spectroscopy (TERS) enabled the structural differences between tau protein aggregates to be revealed, specifically tau protofibrils and young fibrils at the level of individual aggregates.