# Neuropathological correlates of the SMBT-1 PET ligand for imaging astrogliosis in Alzheimer's disease

> **NIH NIH P01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $656,836

## Abstract

Project 4 Summary/Abstract:
The main goal of Project-4 is to provide postmortem neuropathological
evaluation of the recently developed SMBT-1 ligand which, due to high affinity for monoamine oxidase B (MAO-
B), is a novel positron emission tomography (PET) radiotracer for imaging astrogliosis in Alzheimer’s disease
(AD). We propose a series of postmortem studies to determine regional patterns of SMBT-1 binding in relation
to MAO-B, glial fibrillary acidic protein (GFAP), and other markers of reactive astrocytes, as well as amyloid-β
(Aβ) and tau pathology and synaptic loss in cases with different levels of AD neuropathologic changes. We will
accomplish this using autopsy brains banked during previous PPG2&3 cycles, and brains from new PPG4
participants who will be imaged with 18F-SMBT-1 as well as amyloid and tau PET ligands 11C-PiB and 18F-MK-
6240, respectively.
 In Aim 1, we will test the hypothesis that on postmortem brain sections, 3H-SMBT-1 autoradiography and a
novel fluorescent derivative of SMBT-1 (cyano-SMBT-1) correspond strongly to MAO-B/GFAP reactive
astrocytes and are associated more closely with Aβ pathology than tau pathology. Complementary analyses of
frozen brain homogenates from the same regions/cases will characterize 3H-SMBT-1 binding in relation to MAO-
B and GFAP protein levels, Aβ and tau concentrations, and binding levels of 3H-PiB and 3H-MK-6240.
 In Aim 2, we will determine associations of astrogliosis markers, and Aβ and tau pathologies, with regional
synaptic density (a strong correlate of cognition) on postmortem brain sections. Biochemical assays will
determine associations of 3H-SMBT-1 binding, astrogliosis-related proteins, 3H-PiB and 3H-MK-6240 binding
levels, and Aβ and tau concentrations with regional levels of synaptic proteins in the same brain homogenates.
 In Aim 3, we propose the first imaging-to-autopsy validation study of 18F-SMBT-1 PET as an imaging
biomarker of astrogliosis, and its relation to Aβ and tau pathology, in autopsy brains from the PPG4 participants
imaged with 18F-SMBT-1, 11C-PiB, and 18F-MK-6240 PET in Projects 1 and 2. Matching of regions-of-interest
on PET scans and postmortem brain slabs will be optimized using ex-vivo 7T MR imaging of autopsy brains. We
will also determine how postmortem measures of MAO-B/GFAP and aquaporin-4 correlate with region-matched
antemortem analyses of brain fluid dynamics and blood brain barrier using 7T MRI in Project-3. Postmortem
analyses of astrogliosis and cytokines in brain tissues will be correlated with biomarkers of inflammation in blood
samples collected antemortem from the same subjects.
 These studies will involve close interactions of Project-4 with other Projects in the PPG, and will contribute
new knowledge regarding 18F-SMBT-1 PET as a potentially valuable addition to the neuroimaging panel for AD.

## Key facts

- **NIH application ID:** 10410731
- **Project number:** 2P01AG025204-16
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Milos D Ikonomovic
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $656,836
- **Award type:** 2
- **Project period:** 2004-12-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10410731

## Citation

> US National Institutes of Health, RePORTER application 10410731, Neuropathological correlates of the SMBT-1 PET ligand for imaging astrogliosis in Alzheimer's disease (2P01AG025204-16). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10410731. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*