# THE SYNAPTIC TYPE LANDSCAPE OF ALZHEIMER'S DISEASE VISUALIZED BY MULTIPLEX EXPANSION SYNAPTIC NANOSCOPY

> **NIH NIH DP2** · CARNEGIE-MELLON UNIVERSITY · 2022 · $356,860

## Abstract

THE SYNAPTIC TYPE LANDSCAPE OF ALZHEIMER'S DISEASE VISUALIZED BY MULTIPLEX EXPANSION
SYNAPTIC NANOSCOPY
Abstract
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, with high morbidity and mortality
and high costs toward patient care and management, posing a major global public health issue. In addition, the
link between AD and neuroinflammation suggests that this burden may significantly increase in the years
following the COVID-19 pandemic. AD is characterized by memory loss, cognitive decline, and devastating
neurodegeneration associated with synaptic dysfunction and loss. Genome-Wide Association Studies implicate
diverse molecular pathways for human AD disease, but the way that these genetic results relate to synaptic
pathology is unclear. In situ proteomic profiling of synapses across the brain is critical to shed light on potential
mechanisms and therapies. Unfortunately, conventional bulk and single-cell biochemical and sequencing assays
lack spatial resolution for fine-scale synaptic analysis as well as the isolation of discrete synaptic types that may
be differentially affected in AD. Although super-resolution fluorescence imaging methods can offer sufficient
spatial resolution, multicolor imaging is limited to ~4 protein targets due to spectral overlap, which cannot reveal
the convoluted pictures of synaptic pathology in AD. Built upon our innovative molecular imaging platform
supported by the parent DP2, here we propose a nanoscale synapse imaging method that will determine high-
dimensional protein location and protein-protein interactions at synapse in both normal and pathological states
with commercially available reagents, for both clinical AD samples as well as in mouse models of
amyloidogenesis. The outcome of our work will lead to a broadly useful in situ proteomic tool for quantification
of neuronal synapse types available to diverse neuropathology laboratories and will foster a better understanding
of the complexity of molecular mechanisms of AD for development of novel therapeutics.

## Key facts

- **NIH application ID:** 10499537
- **Project number:** 3DP2EB028111-01S1
- **Recipient organization:** CARNEGIE-MELLON UNIVERSITY
- **Principal Investigator:** Yongxin Zhao
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $356,860
- **Award type:** 3
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499537

## Citation

> US National Institutes of Health, RePORTER application 10499537, THE SYNAPTIC TYPE LANDSCAPE OF ALZHEIMER'S DISEASE VISUALIZED BY MULTIPLEX EXPANSION SYNAPTIC NANOSCOPY (3DP2EB028111-01S1). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10499537. Licensed CC0.

---

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