# AMPAR-targeted PET imaging study of Alzheimer's disease

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $190,902

## Abstract

Project Summary: Dysfunction of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is
implicated in the physiopathology of neurological disorders such as schizophrenia and depression, and
neurodegenerative diseases, including Alzheimer’s disease (AD) and its related dementias. A role for AMPAR in AD
was also suggested by the observation that its expression and activity was significantly altered in areas of inflammation
in AD patients and decreased AMPAR expression occurred at the onset of AD. Pharmacological modulation of
AMPAR prevents excessive neuronal activation, representing an attractive therapeutic approach for AD treatment.
Quantification of AMPAR in the living brain, particularly in the AD brain, would enable the assessment of changes and
distribution during disease prognosis, which will provide valuable information for AMPAR-targeted AD
neurotherapeutics.
 As a non-invasive imaging probe, positron emission tomography (PET) is capable of quantifying biochemical
processes in vivo, and a suitable AMPAR probe would substantially improve our understanding of AMPAR-based
ionotropic glutamate signaling under normal and AD conditions otherwise inaccessible by ex vivo (destructive)
analysis. The PI has utilized several PET ligands to measure transmembrane AMPA regulatory proteins activity and
possible aberrant ionotropic glutamate system function in his parent R01 grant. In this AD-focused administrative
supplement application, we aim to evaluate these PET ligands for their ability to non-invasively track transmembrane
AMPA regulatory proteins changes in vivo to monitor AD progression in two transgenic mouse models, followed by
ex vivo biological validation studies in AD mice. The goal of this administrative supplement is to assess the utility of
AMPAR-orientated PET ligands as functional index for AD prognosis and test the specificity and sensitivity of AMPAR-
related protein changes between normal and AD disease states.
 Overall impact: This work will represent a novel PET biomarker study measuring changes of subtype AMPAR
(transmembrane AMPA regulatory proteins) in the AD progression. We expect that this proposed work will not only
help us to differentiate symptomatic from true mechanistic response via PET imaging, but also provide guidance for
AMPAR-based interventions to improve quality of life of AD patients.

## Key facts

- **NIH application ID:** 10123432
- **Project number:** 3R01MH120197-02S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Steven H Liang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $190,902
- **Award type:** 3
- **Project period:** 2019-06-21 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123432

## Citation

> US National Institutes of Health, RePORTER application 10123432, AMPAR-targeted PET imaging study of Alzheimer's disease (3R01MH120197-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10123432. Licensed CC0.

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