# High-Resolution Spatial MIST Technology for Functional Proteomic Study of Neuroinflammation in Alzheimer's Disease

> **NIH NIH R21** · STATE UNIVERSITY NEW YORK STONY BROOK · 2022 · $462,524

## Abstract

Summary
Alzheimer’s disease (AD) is the most common form of dementia and is a looming crisis in the US. Despite
substantial progress made in AD research, the molecular and cellular processes governing neurodegeneration
are still not well understood, and AD therapies have not resulted in significant benefits to patients. The traditional
hallmarks of AD include amyloid beta aggregation and neurofibrillary tangle deposition, while recently
inflammation, an innate immune response in the brain, emerges as a third hallmark. Inflammation particularly
occurs near epicenters of amyloid beta plagues and neurofibrillary tangles, and it involves complicated cellular
interactions that synergize with the progression of neurodegeneration. Understanding the molecular
mechanisms of the functional roles of the cells in neuroinflammation and its influences on neurons is the key to
searching for effective therapeutic targets. Due to the nature of high complexity and spatial heterogeneity, recent
research has vastly turned to next generation sequencing and transcriptomics tools in neurodegeneration studies.
These results on gene expression will still need protein-level validation since proteins carry out most of cellular
functions and biochemical processes. The current multiplexed protein assays on tissue samples are either labor
intensive and low coverage or in low spatial resolution. In this project, we aim to develop a spatial proteomics
technology with cellular resolution to fill the technological gap and timely address the most imperative issues in
AD mechanisms. This technology is built upon a multiplex in situ tagging (MIST) array that measures ~200 AD
relevant proteins from single neurons in our preliminary study. With ~10-100X higher multiplexity than other
spatial protein tools, our spatial MIST will measure most important regulatory proteins and markers in spatially
localized cells of brain sections. Two specific aims we propose include (1) Optimize the experimental techniques
in spatial MIST for detecting 280 key proteins in signaling and regulation of whole mouse brain slices, and (2)
Profile the molecular features of cells near Aβ accumulation and tau enriched regions by spatial MIST during AD
progression. The completion of this project will generate an enabling technology and method widely accessible
in the AD research community to investigate AD pathogenesis from a new, clinically relevant perspective. This
technology will lay the foundation for future mechanistic studies of AD development and identification of potential
therapeutic targets.

## Key facts

- **NIH application ID:** 10343115
- **Project number:** 1R21AG075087-01
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Jun Wang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $462,524
- **Award type:** 1
- **Project period:** 2022-01-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10343115

## Citation

> US National Institutes of Health, RePORTER application 10343115, High-Resolution Spatial MIST Technology for Functional Proteomic Study of Neuroinflammation in Alzheimer's Disease (1R21AG075087-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10343115. Licensed CC0.

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