# Development of PET imaging probes for ROCK2

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $826,482

## Abstract

ABSTRACT
The objective of this project is to develop, validate, and translate novel positron emission tomography (PET)
imaging probes for rho-associated coiled-coil containing protein kinase 2 (ROCK2). Consistent with prior
postmortem studies, significant synaptic loss was found using SV2A PET in the hippocampus and frontal
cortex of patients with MCI and early AD, indicating progressive synaptic loss along the disease path. The
synapse loss in MCI/AD patients is expected to be mediated through activation of rho/ROCK2 signaling
pathway. Elevated ROCK2 has been observed in postmortem brain tissues of asymptomatic AD and MCI
patients and in transgenic rodent models of familial AD. These data demonstrate the potential of detecting
preclinical and prodromal AD through ROCK2 PET imaging, which may lead to identification of new
therapeutic targets with a defined early intervention time window to delay or prevent the synapse loss and
onset of dementia. Therefore, we propose to develop and translate ROCK2 PET imaging probes for future
clinical investigations. Successful completion of this project will yield a ROCK2 PET imaging probe ready to
be tested in humans as a sensitive and quantitative in vivo biomarker for preclinical and prodromal AD,
which will allow early interventions to slow or halt disease progression.

## Key facts

- **NIH application ID:** 10359030
- **Project number:** 5R01AG069921-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Zhengxin Cai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $826,482
- **Award type:** 5
- **Project period:** 2021-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359030

## Citation

> US National Institutes of Health, RePORTER application 10359030, Development of PET imaging probes for ROCK2 (5R01AG069921-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10359030. Licensed CC0.

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