# Relationship between Amyloid beta and Bioenergetics

> **NIH NIH R00** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2020 · $249,000

## Abstract

Project Summary/Abstract
 A clear relationship between amyloid precursor protein (APP), amyloid beta (Aβ), and mitochondria exists.
APP and Aβ influence mitochondrial function, while mitochondrial function and bioenergetic pathways influence
APP processing. Several studies indicate reductions in mitochondrial respiratory flux decrease Aβ production.
Conversely, parameters which increase mitochondrial respiratory flux increase Aβ production. The overall goal
of this study is to determine how bioenergetics influence APP processing pathways. Our preliminary data
support a role for mitochondrial membrane potential and reactive oxygen species (ROS) in modulating the
production of Aβ. Based on these findings, we hypothesize mitochondrial membrane potential and
mitochondrial derived ROS influence APP processing. We will elucidate the involvement of these bioenergetic
intermediates in APP processing pathways and determine how these changes occur. We hypothesize
bioenergetics influence APP processing pathways by modulating the cellular localization and trafficking of
APP, β-, and γ-secretases. To this end our proposed studies will explore fundamental relationships between
mitochondria, energy metabolism-related phenomena, and Aβ production. These studies could potentially
advance our understanding of Alzheimer’s disease (AD)-associated cascades while also providing translational
and relevant insight. Understanding the relationship between Aβ production and bioenergetics will provide
additional clues to the nexus between brain aging and AD, and novel therapeutic targets.
 This K99/R00 award is designed to further Dr. Wilkins’ career path by complimenting her current training
and developing expertise in new areas. These new areas include reprogramming induced pluripotent stem
cells (iPSCs), β-, and γ-secretase biology. At the University of Kansas Medical Center (KUMC), Dr. Wilkins will
work in the neurology department, where the director of the Alzheimer’s Disease Center (Dr. Russell
Swerdlow) is her primary mentor. To facilitate training in new techniques Dr. Wilkins will be assisted by a group
of co-mentors. The co-mentors for this award include: Dr. Kenneth Peterson (KUMC) who will provide
expertise on Crispr/Cas9 systems and reprogramming iPSCs; Dr. Robert Vassar (Northwestern University)
who will provide expertise on β-secretase biology and manipulations, and Dr. Michael Wolfe (Harvard) who will
provide expertise on γ-secretase biology and manipulations. Collaborators will assist with measuring APP
processing (Dr. Bruce Yankner, Harvard) and biostatistical analysis (Dr. Jon Mankhen, KUMC). Dr. Wilkins’
expert mentoring team and collaborators, strong training environment, and prior research experience are
imperative for advancing her career goals.

## Key facts

- **NIH application ID:** 10069474
- **Project number:** 4R00AG056600-03
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Heather M. Wilkins
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2017-08-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10069474

## Citation

> US National Institutes of Health, RePORTER application 10069474, Relationship between Amyloid beta and Bioenergetics (4R00AG056600-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10069474. Licensed CC0.

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