# The Phenotypic Landscape of Cognitive Decline as Revealed by Next-Generation Multiplexed Ion Beam Imaging

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $502,002

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer's disease (AD) is a leading cause of disability and death in the US and a major global public health
problem. Time is running short if we wish to avert a global public health disaster with untold suffering,
disruption of families, and severe challenges to health care systems and economies. Solutions will come only
from innovative research. Genomic studies for late-onset AD (LOAD) have identified over 20 risk loci; however,
translating the relevant molecules identified by genomics to AD-specific mechanistic pathways has been
challenging. Our application, entitled “The Phenotypic Landscape of Cognitive Decline Revealed by Next-
Generation Multiplexed Ion Beam Imaging,” is highly responsive to this urgent scientific need by proposing a
uniquely innovative molecular imaging platform called multiplexed ion beam imaging (MIBI) that will determine
high dimensional protein interactions for AD-relevant molecules identified by genomics studies in normal and
pathological states. Our proposal has three Specific Aims. In Aim 1, we propose to analyze four regions in
healthy aged brains: two sectors of the hippocampal pyramidal layer and from two isocortical regions. Next-
generation MIBI instrumentation will be used to image simultaneously 30+ proteins that mark subtypes of
neurons, synapses, and non-neuronal cells, while covering regulatory signaling, neuro-inflammatory
components, and AD risk gene protein products with subcellular resolution. In Aim 2, we propose to use the
same multiplexed imaging methods in AD brain stratified by APOE genotype. We will analyze these data with
statistical machine learning methods already established in our laboratory, similar to what we have done
previously with different cancers and the immune system. In Aim 3, using infrastructure we have already have
established, we will create a web-based portal where all of the images from this study can be accessed, multi-
color overlays generated ad hoc, and all the features we derive shared freely. We propose a transformative,
collaborative approach to AD that leverages a long-standing NIA-funded longitudinal cohort and is highly
responsive to the National Alzheimer's Plan. These novel insights will illuminate pathways that hold potential
for new therapeutic targets and will create a shared research resource and analysis platform for the community
of scientists committed to developing solutions for AD.

## Key facts

- **NIH application ID:** 10173583
- **Project number:** 5R01AG056287-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Robert michael Angelo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $502,002
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10173583

## Citation

> US National Institutes of Health, RePORTER application 10173583, The Phenotypic Landscape of Cognitive Decline as Revealed by Next-Generation Multiplexed Ion Beam Imaging (5R01AG056287-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10173583. Licensed CC0.

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