# BDNF TrkB- and beta-AR signals in ischemic and non-ischemic cardiomyopathy

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $353,883

## Abstract

Project Summary
Alzheimer’s disease (AD) and heart failure with preserved ejection fraction (HFpHF) are highly
prevalent diseases. Recent findings show the alarming prospective that they can intertwine in the
same individuals. For both conditions, the therapeutic options remain scant. Following the NIH
initiative directed to penetrate the pathogenesis of either of these diseases to unearth more
effective therapeutic options, here we propose to investigate a new mechanism that AD and
HFpEF may have in common and that can unveil a unifying therapeutic approach for both
diseases. That is: that the concomitant cardiac and central loss in brain-derived neurotrophic
factor (BDNF) and its associated receptor, tropomyosin receptor kinase B (TrkB) accounts for Aβ
pathology and hyperphosphorylated tau deposition and vice-versa, contributing to the onset and
progression of AD and HFpHF. In turn, these two conditions negatively reverberate on each other.
Here, we propose two aims. In the first Aim, using unique gene-edited mouse lines for cardiac
and neuronal BDNF/TrkB signaling, we will determine whether a lack of TrkB/BDNF signaling
fuels Aβ and/or tau pathology, triggering HFpEF and, in turn, the accumulation of Aβ and/or tau
in the heart underlies HFpEF pathogenesis via reduced expression of TrkB/BDNF signaling. In
the second Aim, we will test the impact of specific, agonist-based TrkB stimulation prevents the
accumulation of Aβ and hyperphosphorylated tau in the heart and brain of AD, improving both
cognitive/locomotor and diastolic dysfunction.Of note, in the present proposal, we will put the
evaluation of myocardial performance on equal footing with that of central functions. Indeed, in all
mouse protocols performed here, we will conduct behavioral studies apt to evaluate cognitive
abilities (such as short- and long-term memory) and mood control (anxiety and depression) to
determine whether an improvement of cardiac function via TrkB agonists attenuates behavioral
alterations typically found in patients with AD or HFpEF, or vice versa. The functional parameters
will be also paralleled by the biochemical and pathological assessment, key for the diagnosis of
proteinopathies and for the analysis of the mechanisms.

## Key facts

- **NIH application ID:** 10287657
- **Project number:** 3R01HL136918-04S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Nazareno Paolocci
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $353,883
- **Award type:** 3
- **Project period:** 2018-01-11 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287657

## Citation

> US National Institutes of Health, RePORTER application 10287657, BDNF TrkB- and beta-AR signals in ischemic and non-ischemic cardiomyopathy (3R01HL136918-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10287657. Licensed CC0.

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