# Incorporating Spatial Proteomics to Understand the Basis of Hyper and Hypoconnectivity in mouse models of AD

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $782,443

## Abstract

In this proposal, we propose studies to elucidate the basis of the hyper and hypoconnectivity observed in AD.
We will combine high resolution in vivo MRI imaging strategies with state-of the-art spatial proteomics. By
combining these methods, we will obtain these two types of data in the same animal, allowing us to incorporate
machine learning (ML) to build a model to define spatially distinct protein expression changes in regions of hyper
and hypoconnectivity over time. A recent MRI/PET imaging study suggested that tau tangles are responsible for
hypoconnectivity, while Ab plaques are responsible for hyperconnectivity. This intriguing hypothesis, based on
data from a heterogeneous group of patients, needs to be tested under carefully controlled conditions that can
only be obtained using animal models of AD. PET imaging identifies tau tangles and Ab plaques but cannot
determine which phosphorylated tau (p-tau) species are driving hypoconnectivity, nor can it determine the
contribution of soluble Ab42 to the hyperconnectivity. In the studies proposed in this application, we will test three
hypotheses: 1) Soluble Ab42 accumulation causes regions of hyperconnectivity. 2) A subset of soluble p-tau
species is responsible for hypoconnectivity. 3) Regions of hyper and hypoconnectivity exhibit distinct spatial
proteomic profiles that reflect early and late phases of the disease.

## Key facts

- **NIH application ID:** 10797359
- **Project number:** 1R01AG081192-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** ROBIA G PAUTLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $782,443
- **Award type:** 1
- **Project period:** 2024-06-15 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10797359

## Citation

> US National Institutes of Health, RePORTER application 10797359, Incorporating Spatial Proteomics to Understand the Basis of Hyper and Hypoconnectivity in mouse models of AD (1R01AG081192-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10797359. Licensed CC0.

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