# Imaging Networks of Affective Behaviors and Dopamine in Alzheimer's Disease

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2020 · $406,313

## Abstract

ABSTRACT
Apathy is diagnosed in approximately 70% of patients with dementia, including Alzheimer’s disease (AD).
Changes in affective expression and reduced motivation towards daily activities is thought to involve deficits in
synaptic communication between mesolimbic dopamine (DA) circuitry and hippocampus of AD patients. Our
central hypothesis is that overexpression of β-amyloid protein (Aβ) or hyperphosphorylated tau (p-tau) reduces
neuronal activity between dorsal hippocampal CA1 (dHC-CA1), nucleus accumbens and the DA-enriched
ventral tegmental area (VTA). This is predicted to be linked to reduced reward-seeking and sociability and is
rescued by drugs that increase brain DA levels. The proposed research will employ high-field resting state
functional magnetic resonance imaging (rsfMRI), network analysis, functional tracer-based MRI (MEMRI), and
assessment of non-cognitive (affective) behaviors in Aβ or p-tau overexpressing mice to clarify the effects of
DA drugs on reward and cognitive network activity. We will investigate the functional brain and behavioral
responses to two compounds with therapeutic value for apathy and other non-cognitive affective conditions in
AD, the DA reuptake inhibitor methylphenidate and the monoamine oxidase B (MAO-B) inhibitor selegiline. To
test our central hypothesis, we will: (1) determine how drugs that block DA reuptake or inhibit DA breakdown
affect reward-seeking and sociability in Aβ-expressing TgCRND8 mice and tau-expressing rTg4510 mice (aim
1), (2) investigate how these two drugs alter functional connectivity between mesolimbic and cognitive brain
networks of TgCRND8 and rTg4510 mice (aim 2), and (3) determine the effect of these DAergic agents on in
vivo calcium-dependent synaptic activity between the VTA and dHC-CA1 of TgCRND8 and rTg4510 mice (aim
3). We will combine cutting edge high field rsfMRI, quantification of network analysis metrics with biomarker-
like properties and will apply circuit-specific contrast-based synaptic activity mapping in mice bearing human
AD mutations that produce well-defined plaque or tangle pathology. From a public health perspective, the
proposed studies will provide new insight on non-cognitive aspects of AD. It will contribute to clarifying the
effects of Aβ or p-tau on functional network activity and on specific dHC-CA1 circuits, and in relation to
reward/affective behaviors.

## Key facts

- **NIH application ID:** 9874277
- **Project number:** 1R21AG065819-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** MARCELO FEBO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $406,313
- **Award type:** 1
- **Project period:** 2020-02-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9874277

## Citation

> US National Institutes of Health, RePORTER application 9874277, Imaging Networks of Affective Behaviors and Dopamine in Alzheimer's Disease (1R21AG065819-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9874277. Licensed CC0.

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