AGE-DEPENDENT STUDY OF PATHOLOGICAL PROGRESSION OF ALZHEIMER’S DISEASE IN HIPPOCAMPAL AND CORTICAL TISSUE OF HUMAN AND AN AD MOUSE MODEL

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Taylor A Leposa (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Degeneration of synaptic plasticity plays a critical role in Alzheimer’s disease (AD) pathogenesis. Recent studies have suggested that neuroinflammation may contribute to this degeneration by disrupting the amyloid metabolism and by microglial overgrowth. This study aims to investigate the pathological progression of AD hippocampal and cortical tissues of human and an AD mouse model. To examine the amyloid and microglial activity in the human brain, we acquired brain tissues from clinically diagnosed AD and non-dementia (ND) patients. To examine this activity in the mouse model, we acquired brain tissues from age-matched wild type (WT) and AD affected (3xTg-AD) mice in 4, 6, 8 and 12-month age groups. Immunohistochemical (IHC) analysis was utilized to determine the characteristics of pathological AD hallmarks. Analysis of the human brain tissue showed an alteration in amyloid precursor protein (APP) in the hippocampus of AD patients as compared to the ND patients. The activation of microglial cells in the AD patients was increased, which indicates neuroinflammation. Results of mouse brain tissue analysis indicated a heightened proliferation of microglial cells in the CA3 region (*p<0.05) of the hippocampus in the 6-month-old 3xTg-AD male mice. Additionally, results indicated hyper-proliferation of microglial cells in multiple regions of the hippocampus in 8-month-old 3xTg-AD female mice, (*p<0.05). Moreover, increased presence of amyloid burdened neurons was observed in both the cortical and amygdala regions of 4, 6, 8, and 12-month age groups of 3xTg-AD mice as compared to their age-matched WT. Phosphorylated tau protein (pTau) was additionally found to be increased in the 3xTg-AD male mice as compared to their 3xTg-AD female counterparts in multiple age groups. Neuroinflammation and aberrant activity of microglial proliferation contribute to the progression of AD. The ability to understand, and therefore modulate, neuroinflammation may be a promising approach for prevention of progression in AD.

Additional Information

Publication

Thesis

Language: English

Date: 2023

Subjects

Alzheimer's disease;progression

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