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All ETDs from UAB

Theses/Dissertations

2020

Alzheimer's disease

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Locus Coeruleus Degeneration In Alzheimer’S Disease And Its Effect On Beta-Adrenergic Signaling In The Hippocampus, Bethany Langner Jan 2020

Locus Coeruleus Degeneration In Alzheimer’S Disease And Its Effect On Beta-Adrenergic Signaling In The Hippocampus, Bethany Langner

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Locus coeruleus (LC) degeneration in Alzheimer’s Disease (AD) and loss of noradrenergic (NA) innervation in hippocampus contributes to learning and memory deficits. Recently, a novel rat model (TgF344-AD) has been created that allows for a more thorough investigation into these mechanisms due to its similarity to human AD pathology. The McMahon lab has recently demonstrated heightened long-term potentiation (LTP) and a ‘supersensitivity’ of -adrenergic receptors (-ARs) at excitatory synapses in the dentate gyrus (DG) in TgF344-AD rats. These mechanisms could be responsible for maintaining learning and memory during buildup of AD pathology. The first goal of this Master’s thesis was …


Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk Jan 2020

Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk

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Alzheimer’s disease (AD) is the leading neurodegenerative disorder that affects an astonishing 5.8 million Americans, a number projected to reach 14 million by the year 2050. While only about 1% of all AD cases are caused by mutations in APP, PSEN1, and PSEN2, the cause of sporadic AD remains unknown. Variations in several risk genes have been proposed to contribute to the development of sporadic AD cases. Since, currently, there are no disease-modifying therapies for families affected by AD and multiple anti-amyloid-beta therapies failed in clinical trials, determining how these risk genes contribute to the development of AD is crucial …


Self-Awareness Of Functional Deficits In Older Adults With Mild Cognitive Impairment, Kayla Ann Steward Jan 2020

Self-Awareness Of Functional Deficits In Older Adults With Mild Cognitive Impairment, Kayla Ann Steward

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Performance of instrumental activities of daily living (IADLs) can become compromised in older adults with mild cognitive impairment (MCI). Poor self-awareness of deficits, also known as anosognosia, occurs in a substantial minority of those with MCI and varies in extent depending on the domain examined. This dissertation attempts to explain the inter- and intra-patient variability in anosognosia by examining (1) differences in objective IADL performance and self-awareness of functional difficulties between those with amnestic single- (-ASD) and multi-domain (-AMD) MCI, and by examining (2) the neuropsychological and (3) neuroanatomical correlates of anosognosia for IADLs in older adults across a broad …


Denervation Supersensitivity Of Βeta-Adrenergic Receptors In A Prodromal Model Of Alzheimer's Disease, The Tgf344-Ad Rat, Anthoni Goodman Jan 2020

Denervation Supersensitivity Of Βeta-Adrenergic Receptors In A Prodromal Model Of Alzheimer's Disease, The Tgf344-Ad Rat, Anthoni Goodman

All ETDs from UAB

The central noradrenergic (NA) system is critical for maintenance of attention, behavioral flexibility, spatial navigation, and learning and memory, those cognitive functions lost first in early Alzheimer’s disease (AD). In fact, the locus coeruleus (LC), the major source of norepinephrine (NE) in brain, is the first site of pathological tau accumulation in human AD associated with axon loss throughout forebrain, including hippocampus. The dentate gyrus (DG) is heavily innervated by LC-NA axons, where released norepinephrine (NE) acts on β adrenergic receptors (ARs) at excitatory synapses from entorhinal cortex (EC) to facilitate long-term synaptic plasticity and memory formation. These synapses show …