Item Details

abstract

Alzheimer’s disease currently affects an estimated 6.5 million people in the US, but the underlying mechanisms that trigger pathology remain unclear and available therapies do not stop disease progression. There is a definite need to understand the impact of molecular processes, such as mitochondrial bioenergetics, on disease pathology. Our lab and others use circulating blood cells such as platelets, PBMCs, and monocytes to assess systemic mitochondrial bioenergetics based on the premise that circulating and extrinsic factors influence bioenergetic capacity throughout the body. In particular, our lab has demonstrated that blood cell bioenergetics correlate to brain bioenergetics and FDG-PET measures of brain glucose uptake. However, the effect of circulating factors on the brain and peripheral bioenergetics in AD is poorly understood. This work aims to clarify the role of three circulating and extrinsic factors, diet, lipids, and neuronally derived exosomes, on bioenergetics in the context of AD. Chapter 2 demonstrates that two circulating factors, glucose and insulin, were related to disrupted bioenergetic patterns between brain regions in cynomolgus macaques fed a Western diet compared to animals fed a diet Mediterranean diet, especially in two brain regions important in AD pathology. Chapter 3 describes how circulating factors in plasma can affect bioenergetics in neurons based on cognitive status and identifies two lipids as potential mediators of bioenergetics in Alzheimer’s dementia. Chapter 4 describes how circulating exosomes of neuronal origin from participants across the cognitive spectrum increase in-vitro neuron respiration with decreasing cognition. Taken together, these studies provide evidence that extrinsic factors, such as poor diet, and circulating factors such as lipids and exosomes, can mediate neuronal and systemic bioenergetics.

subject

Alzheimer's

Bioenergetics

Diet

Exosomes

Lipids

Mitochondria

contributor

Amick, Kimberly Allison (author)

Molina, Anthony J. A. (committee chair)

Deep, Gagan (committee member)

Macauley-Rambach, Shannon (committee member)

Olivier, Michael (committee member)

Craft, Suzanne (committee member)

date

2022-07-11T19:17:41Z (accessioned)

2022 (issued)

degree

Neuroscience (discipline)

2024-05-23 (liftdate)

embargo

2024-05-23 (terms)

identifier

http://hdl.handle.net/10339/101025 (uri)

language

en (iso)

publisher

Wake Forest University

title

DIET, CIRCULATING FACTORS, AND EXOSOMES MEDIATE NEURONAL AND SYSTEMIC BIOENERGETICS

type

Dissertation