# SV2A PET imaging in Alzheimer's Disease

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $1,133,380

## Abstract

ABSTRACT
Synaptic loss is a major feature of symptomatic Alzheimer’s disease (AD). New positron emission tomography
(PET) radioligands have been developed which bind to synaptic vesicle glycoprotein 2A (SV2A), a synaptic
vesicle protein found in presynaptic nerve terminals throughout the brain. While development of these tracers is
a major advance for the field of AD, very little is yet known about synapse loss across the clinical and pathological
spectrum of AD, and longitudinal studies in large cohorts are lacking. In order to address this gap in knowledge,
we propose to perform longitudinal SV2A PET imaging with [C-11]UCB-J in participants recruited from the
Wisconsin Alzheimer’s Disease Research Center. The sample will include cognitively unimpaired AD biomarker
negative participants, cognitively unimpaired biomarker positive participants, individuals with mild cognitive
impairment (MCI), and participants with dementia due to AD. Participants will be imaged at baseline and at two-
year follow-up. The hypothesis is that regional synaptic loss will serve as a sensitive marker of
neurodegeneration in the context of plaque and tangle accumulation and will explain cognitive decline. In order
to address this hypothesis, we propose the following three specific aims: 1) determine the extent to which [C-
11]UCB-J provides unique information from MRI regarding neurodegeneration; 2) determine the rate of synapse
loss as reflected by [C-11]UCB-J signal; and 3) determine the extent to which [C-11]UCB-J associates with
cognitive decline. In addition to [C-11]UCB-J PET, we will acquire [C-11]PIB PET to determine spatial amyloid
plaque burden, as well as [F-18]MK6240 PET to determine tau tangle burden. This study will be the first to obtain
these three markers in tandem, which will allow—for the first time—the ability to determine how these pathologies
evolve in AD, and determine how they are spatially and temporally related to one another. The National Institute
on Aging has called SV2A PET imaging a “potentially game-changing biomarker in AD and AD-related
dementias”. Synapse loss is expected to be the most closely associated with cognitive decline, yet no large
human studies have yet been undertaken to examine regional synapse loss across the spectrum of AD. The
proposed project addresses this gap in knowledge. This program of research is expected to improve early
detection of AD, improve prediction of cognitive decline, and inform the development of new treatment strategies.

## Key facts

- **NIH application ID:** 9919489
- **Project number:** 5R01AG062285-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Barbara Brigitta Bendlin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,133,380
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9919489

## Citation

> US National Institutes of Health, RePORTER application 9919489, SV2A PET imaging in Alzheimer's Disease (5R01AG062285-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9919489. Licensed CC0.

---

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