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An Investigation Of Hhv6'S Impact On The Cognitive Progression And Microglial Changes In An Alzheimer's Disease Cohort, Charles E. Seaks Jan 2022

An Investigation Of Hhv6'S Impact On The Cognitive Progression And Microglial Changes In An Alzheimer's Disease Cohort, Charles E. Seaks

Theses and Dissertations--Physiology

The role of herpesviruses and, more specifically, HHV6 in the development of Alzheimer’s disease (AD) and associated cognitive decline is still being investigated. High ubiquity and prevalence in the population have led to a high degree of skepticism about HHV6 as a potential contributor to cognitive decline and dementias. However, recent evidence related to another herpesvirus, herpes simplex virus 1, suggests that reactivation, not carriage, of the virus may be the key factor to explain the dissonance between the virus’ ubiquity and contributions to dementias. With that in mind, we set out to assess cases from the Sanders-Brown Center on …


Evaluating The Role Of Mmp9 In Hyperhomocysteinemia Induced Cerebrovascular Pathology, Alexandria Linton Jan 2022

Evaluating The Role Of Mmp9 In Hyperhomocysteinemia Induced Cerebrovascular Pathology, Alexandria Linton

Theses and Dissertations--Neuroscience

Vascular contributions to cognitive impairment and dementia (VCID) is one of the leading causes of dementia, along with Alzheimer’s disease (AD), and often manifests as a comorbidity of AD. Elevated plasma homocysteine, known as hyperhomocysteinemia (HHcy), is a risk factor for VCID; however, the mechanism underlying the connection between HHcy and development of VCID pathology remains elusive. Understanding this mechanism would reveal novel therapeutic targets with the potential to be disease modifying, which are a critical need for a disease that lacks any approved treatment. Previous studies from our lab have strongly associated neuroinflammation and blood brain barrier (BBB) dysregulation …


Uncovering The Role Of Apoe4 On Alzheimer’S Disease-Related Neuroinflammation, Courtney Marie Kloske Jan 2022

Uncovering The Role Of Apoe4 On Alzheimer’S Disease-Related Neuroinflammation, Courtney Marie Kloske

Theses and Dissertations--Physiology

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by two hallmark pathologies: amyloid-beta plaques (Ab plaques) and hyperphosphorylated, aggregated tau tangles. These pathologies are typically accompanied by the presence of neuroinflammation which is primarily mediated by microglia. Interestingly, several genetic risk factors that increase the risk of AD also have direct impacts on neuroinflammation. Of interest, Apolipoprotein E (ApoE) is the largest genetic risk factor for AD. ApoE has three isoforms- E4 confers an increased risk for AD, E3 is considered the “control” phenotype, and E2 is protective against AD. E4 plays a role in virtually …