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
Quantum Material Multilayer Photonic Devices and Network
Summary Realizing highly integrated quantum photonic devices on a chip can enable new opportunities for photonic quantum computation. In this project, we explore heterostructures of stacked two-dimensional (2D) materials, such transition metal dichalcogenides (TMDC) or graphene, combined with optical microcavities as a platform for such devices. 2D materials are extremely thin and flexible, and have […]
December 12, 2019
Line-Scanning optical coherence tomography system for in-vivo, non-invasive imaging of the cellular structure and blood perfusion of biological tissue
Summary Optical coherence tomography (OCT) is an optical imaging method that allows for in-vivo, non-invasive imaging of the structure and vasculature of biological tissue. Commercially available, clinical OCT systems utilize point-scanning method to acquire volumetric images over a large surface with typical frame rates of ~ 30 frames/ second. Since living biological tissue is constantly […]
August 27, 2019
Rydberg Atom Array Quantum Simulator
Summary Quantum simulators enable probing the static and dynamic properties of correlated quantum many-body systems that would otherwise be numerically inaccessible using classical simulators. We are developing quantum simulators based on arrays of neutral atoms excited to Rydberg states. Such Rydberg atom arrays are advantageous for simulating the dynamics of interacting spin systems (Ising spin […]
February 27, 2020
Harnessing the Promise of Quantum Materials for Future Electronic Devices
Summary Two-dimensional (2D) quantum materials, such as graphene and molybdenum disulfide, have great potential for use in future flexible and wearable electronics applications. With traditional silicon-based electronics nearing their theoretical performance limits, nano-electronics made from 2D quantum materials offer breakthrough opportunities for energy-efficient, wearable ubiquitous computation. In this project, we will study integration of […]
June 14, 2018