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Peripheral Metabolic Disruptions Drive Sleep Impairments : = Implications for the Pathophysiology of Alzheimer's Disease.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Peripheral Metabolic Disruptions Drive Sleep Impairments :/
Reminder of title:	Implications for the Pathophysiology of Alzheimer's Disease.
Author:	Carroll, Caitlin M.
Description:	1 online resource (236 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 84-07, Section: B.
Contained By:	Dissertations Abstracts International84-07B.
Subject:	Nanoscience. -
Online resource:	click for full text (PQDT)
ISBN:	9798368468662

Peripheral Metabolic Disruptions Drive Sleep Impairments : = Implications for the Pathophysiology of Alzheimer's Disease.
Carroll, Caitlin M.

Peripheral Metabolic Disruptions Drive Sleep Impairments :Implications for the Pathophysiology of Alzheimer's Disease. - 1 online resource (236 pages)

Source: Dissertations Abstracts International, Volume: 84-07, Section: B.

Thesis (Ph.D.)--Wake Forest University, 2023.

Includes bibliographical references

With no FDA-approved disease modifying treatments available, and an aging general population, Alzheimer's disease (AD) is a growing public health crisis. Individuals with type 2 diabetes (T2D), a disease also associated with aging, have an increased risk of AD. Despite the rising prevalence of both disease, the underlying mechanisms connecting their pathophysiology is unknown. The chapters in this dissertation consider sleep as a link between glucose dysregulation and amyloid-β pathology. Specifically, we use acute modulation of peripheral glucose to understand the impacts on cerebral metabolism and neuronal activity, which can ultimately alter sleep. We also evaluate the independent impacts of age and Aβ pathology on peripheral and cerebral glucose homeostasis. Further, we used a high fat, high sugar diet and metformin treatment to bidirectionally modulate peripheral glucose levels and alter sleep independent of changes in pathology. First, we established a metabolic signature of sleep-wake that is defined by a conserved, temporal relationship between ISF glucose and lactate. We then demonstrated this relationship is disrupted by acute hyper and hypoglycemia (Chapter 2). Next, we showed peripheral glucose dysregulation, as caused by HFD/HSW or Aβ pathology, is sufficient to disrupt diurnal rhythms of cerebral metabolism and neuronal activity (Chapters 3-4). Ultimately, this leads to impaired slow wave sleep. Finally, we demonstrated rescuing peripheral glucose homeostasis with metformin treatment can normalize diurnal rhythms and slow wave sleep (Chapter 4). Collectively, we identified a cyclic relationship between peripheral glucose homeostasis and sleep, both modifiable risk factors in the progression of AD. Moreover, we showed modulating peripheral glucose homeostasis directly impacts cerebral metabolism and neuronal activity, ultimately affecting slow wave sleep. This provides an explanation for the elevated risk of AD in individuals with T2D and highlights potential therapeutic targets for mitigating this risk.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798368468662Subjects--Topical Terms:

632473
Nanoscience.
Subjects--Index Terms:

Sleep impairmentsIndex Terms--Genre/Form:

554714
Electronic books.

Peripheral Metabolic Disruptions Drive Sleep Impairments : = Implications for the Pathophysiology of Alzheimer's Disease.
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