# MIRIAD - Multiplexed Imaging of Resilience In Alzheimers Disease

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $865,036

## Abstract

ABSTRACT
Alzheimer's disease (AD) remains a leading cause of disability and death in the US and major global public
health problem due to rise in aging population resulting in untold suffering, and severe challenges to health
care systems and economies is certain. Solutions will come only from innovative research. Our application is
highly responsive to this urgent scientific need by proposing to leverage an innovative molecular imaging
platform invented at Stanford, multiplexed ion beam imaging (MIBI). We will determine the high dimensional
cellular and subcellular protein-level expression, interaction, and localization for AD-relevant molecules
identified by genomic and proteomic studies in resilience and pathologic states using human brain sections
from an ongoing proteomic investigation of AD. We hypothesize that in-depth, stage-specific phenotypic
signatures extracted from these unique groups will provide insight into the modifiable factors that endorse the
protective mechanisms of brain reserve. We will test our hypothesis through three Specific Aims: (1) Establish
a subcellular, phenotypic framework of vulnerable and resistant brain areas. Next-generation MIBI equipment
will be used to rigorously image 30+ proteins simultaneously; targets marking subtypes of neurons, synapses,
non-neuronal cells, neuro-inflammatory, and vascular components will be concurrently measured. (2) Reveal
cognitive resilience multiplexed phenotypes. Using approaches we have successfully applied in other single
cell studies, we will analyze multiplexed imaging data with statistical deep learning methods already
established in our lab to identify topological, cellular, and molecular phenotypic differences among resilient, co-
morbid, and AD dementia. (3) Implement a shared data repository. The power of multiplexed imaging in
biology is its ability to reveal co-localization or mutual exclusivity to infer regulatory roles and gain mechanistic
insight. To disseminate hundreds of these images from our proposed highly multiplexed study, we will create a
web-based portal, using already established infrastructure, where all of the images from this study can be
accessed, multi-color overlays generated ad hoc, and all the features will be shared freely.

## Key facts

- **NIH application ID:** 10212937
- **Project number:** 5R01AG057915-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Robert michael Angelo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $865,036
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212937

## Citation

> US National Institutes of Health, RePORTER application 10212937, MIRIAD - Multiplexed Imaging of Resilience In Alzheimers Disease (5R01AG057915-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10212937. Licensed CC0.

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