# Evaluating microtubule binding as a potential imaging biomarker for Alzheimer's disease

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2020 · $499,595

## Abstract

Project Summary/Abstract
Impairment of neuronal microtubules resulting from hyper-phosphorylation of the tau proteins is implicated in
many disease pathologies including Alzheimer's disease (AD), Parkinson disease and other neurological
disorders. However, there
techniques.
(PET)
indicates
neurodegeneration
way
are no reliable noninvasive methods to quantify microtubules using clinical imaging
key unanswered question is whether the quantitative nature of Positron Emission Tomography
harnessed to measure in vivo concentrations of microtubules. Increasing scientific evidence
microtubule stabilizing agents provides protective benefits against the deleterious effects of
in treating AD. However, quantifying these protective benefits is difficult, since there is no
to directly probe their interactions with microtubules.
 A
can be
that
Our goal is to develop in vivo imaging of microtubules
using our novel PET probes, at all stages of AD progression. Thus we propose 3 Specific Aims based on our
strong preliminary data. In Aim 1, we will determine the relationship between microtubule integrity and amyloid
β pathology by performing longitudinal microPET/CT imaging of microtubules with [11C]MPC-6827 and amyloid
β imaging with [11C]PiB in two murine models of AD. In Aim 2, we will quantify and characterize microtubule
uptake in brains of the same murine models of AD using [3H]/[11C]MPC-6827. We will perform ex vivo
biodistribution, in vitro autoradiography and histopathological assays to correlate microtubule density with
routine neurobiomarkers. In Aim 3, we will determine and establish dependency of microtubule imaging uptake
to amyloid β and/or tau levels after therapeutic interventions. We will perform microPET/CT images in the
same two murine models of AD, before, during and after the standard treatment protocols with potential
therapeutic agents reducing amyloid β and/or tau levels. In this project, led by an Early Stage Investigator, we
hypothesize that we can expand the microtubule scaffold as potential in vivo imaging agents, not only to
diagnose AD at an early stage, but also follow the therapeutic utility of the treatments. The PET imaging data
generated could be a valuable tool for clinicians to assess AD in several stages of progression and treatment.
This project is the first to propose the imaging of microtubules in vivo in AD. If successful, this work will provide
a new paradigm to directly probe microtubules in vivo in real time. Our work could markedly enhance precision
medicine approaches for treatment of AD and other neurodegenerative diseases.

## Key facts

- **NIH application ID:** 9866005
- **Project number:** 1R01AG065839-01
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Kiran Solingapuram Sai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $499,595
- **Award type:** 1
- **Project period:** 2020-01-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9866005

## Citation

> US National Institutes of Health, RePORTER application 9866005, Evaluating microtubule binding as a potential imaging biomarker for Alzheimer's disease (1R01AG065839-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9866005. Licensed CC0.

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