# Super-Resolution Microscopy of Small Quantum Dots to Elucidate the Mechanisms of Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $674,050

## Abstract

PROJECT SUMMARY / ABSTRACT
Alzheimer's disease (AD) afflicts more than 5 million Americans, yet no known drug is able to prevent or stop
the disease. Before AD fully develops with insoluble amyloid-β plaque deposits and neurodegeneration, there is
a progressive cognitive decline associated with the impairment of synaptic plasticity that underlies learning and
memory. This abnormal synaptic plasticity is likely caused by soluble amyloid-β oligomers affecting the synaptic
levels of AMPA and NMDA receptors, two glutamatergic receptors that mediate induction and expression of
synaptic plasticity. However, the underlying detailed mechanisms are not known and are exceptionally
challenging to study due to the complex behavior of these receptors and the small nanometer-scale dimensions
of the synaptic domains in which they reside.
The goal of this proposal is to understand the molecular details of abnormal synaptic plasticity present in early
AD by developing small nanoparticle-based optical probes and new microscopy techniques to analyze the
position and dynamics of AMPA and NMDA receptors in normal and AD brains. This goal will be accomplished
through the individual and collective efforts of three principle investigators, Paul Selvin (microscopy), Andrew
Smith (quantum dots) and Hee Jung Chung (neurobiology). They have previously worked as a team to publish
two manuscripts on generating small quantum dots (sQD) (< 10 nm diameter) that can enter the neuronal
synapse and accurately follow the receptor number and dynamic placement in dissociated cultured neurons.
To achieve this goal, Aim 1 will optimize super-resolution imaging techniques for sQDs in dissociated
hippocampal culture and thick hippocampal slices with intact circuitry, specifically focusing on 1- and 2-photon
excitation with FIONA and PALM/STORM microscopy. This will allow < 20 nm resolution in all three dimensions.
Aim 2 will develop a novel set of sQDs that are smaller, stable, and monovalent with minimal non-specific
interaction with tissue. Aim 3 will apply sQDs and super-resolution optical methods to perform single-molecule
imaging of glutamate receptors during synaptic plasticity in hippocampal culture and acute slices from wild-type
and AD transgenic model mice. Because of our on-going successful collaboration, we are able to work with the
AD model immediately, while new microscopy and quantum dots are being generated. This research will
increase our understanding of the early pathogenesis of AD and therefore foster the development of new
therapeutic strategies that could specifically inhibit the progression of cognitive decline of this disease.

## Key facts

- **NIH application ID:** 9918990
- **Project number:** 5R01NS097610-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Hee Jung Chung
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $674,050
- **Award type:** 5
- **Project period:** 2016-05-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918990

## Citation

> US National Institutes of Health, RePORTER application 9918990, Super-Resolution Microscopy of Small Quantum Dots to Elucidate the Mechanisms of Alzheimer's Disease (5R01NS097610-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9918990. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*