Specific tests for Alzheimer’s disease (AD) diagnosis are currently unavailable, despite AD being the leading cause of dementia. One hallmark of AD progression is the aggregation of tau proteins into paired helical filaments and neurofibrillary tangles, which is accelerated by the hyperphosphorylation of Tau proteins. However, the mechanism by which the hyperphosphorylated tau accelerates protein aggregation is not completely understood. Furthermore, detecting and disrupting such aggregated forms through the blood-brain barrier (BBB) remains a significant bottleneck in developing AD diagnostics and therapeutics. At the same time, quantum dots (QDs) have shown tremendous potential in penetrating the BBB to diagnose brain cancer, as well as detecting and disrupting protein aggregates in other neurodegenerative diseases such as Parkinson’s disease. QDs are an attractive diagnostic material due to their fluorescence-emitting capabilities, nanoscale size that allows penetration of the BBB, chemical stability, solubility, and facile synthesis. However, QDs have not yet been assessed for their ability to detect and disrupt hyperphosphorylated tau tangles. Hence, the aims of this project are two-fold: 1) to unravel the mechanisms and energetic barriers of normal and hyperphosphorylated tau protein aggregation by building three-dimensional atomistic models of aggregated structures and performing classical and enhanced sampling molecular dynamics simulations on these models; 2) to predict the potential of QDs in binding to and disrupting hyperphosphorylated tau tangles though polarized ligand docking and free-energy calculations. Upon identification of potential QD-binding signatures, these QDs will be synthesized and tested in vitro and in vivo through collaborative efforts with the goal of translating this work into clinical diagnostic applications for AD in the future.
Figure 1. Microtubule-associated protein tau (MAPT) functions in the healthy brain (left) and a brain with Alzheimer’s disease (AD) (right). Self-association and excessive post-translational modifications of Tau proteins result in the formation of neurofibrillary tangles and cause neurodegeneration in AD patients. Targeting the tau aggregates using Quantum Dots could help develop potential diagnostics and/or therapeutics for AD.
Related Content
Next Generation Quantum Sensors
We are developing new semiconductor p-n junctions and designing novel nanowire arrays that have the potential to significantly enhance the ability to detect light at the single photon level over an unprecedented wavelength range from the ultraviolet to infrared.
June 1, 2017
Photonic Quantum Processor
Photonic quantum processors based on integrated quantum photonic circuits require entangled photon pairs to perform quantum computations. However, current state-of-the-art technologies utilize probabilistic entangled photon sources with limited pair-extraction efficiencies, negatively affecting the computation speed. This project aims to boost the speed of on-chip quantum operations by using bright, on-demand entangled photon sources with an […]
April 24, 2023
Ultrafast Dynamical Studies of Valley-Based Qubits
Summary As monolayers, transition metal dichalcogenides (TMDCs) – such as tungsten diselenide (WSe2) – become direct-bandgap semiconductors capable of emitting light. Compared to conventional direct-bandgap semiconductors, such as III-V semiconductors like GaAs, excitons (quasiparticles made of an electron hole bound with an electron) and single-layer TMDCs (SL-TMDCs) have much stronger binding energy. Excitons and […]
June 29, 2018
Quantum Dynamics of Cavity Interactions with Spin Ensembles
Summary High quality factor cavities can be powerful control elements for ensembles of spins, enabling unitary control as well as on demand cooling. They can also be used to couple two otherwise non-interacting ensembles. The goal of the project is to explore the physics and engineering of such systems both theoretically and experimentally. The laboratory contains a […]
September 7, 2016