Date of Award

1-1-2022

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Biological Sciences

Content Description

1 online resource (iv, 28 pages) : illustrations (some color)

Dissertation/Thesis Chair

Annalisa Scimemi

Committee Members

Kristen Zuloaga, Sara Lagalwar

Keywords

Amyloid beta-protein, Alzheimer's disease, Neural transmission

Subject Categories

Neuroscience and Neurobiology

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease affecting 4.5 million people in the US, a number expected to increase 3-fold over the next 30 years. One of the hallmarks of AD is the extracellular accumulation of the protein Aß₄₂ throughout in the brain, particularly in limbic structures like the temporal cortex and hippocampus, key regions for learning and memory. Currently available animal models for AD aim to reproduce key genetic traits of the familial variant of the disease, but >90% of AD patients are affected by idiopathic AD. To overcome this potential limitation, we use a different approach to study AD, based on the use of viral induction of Aß₄₂ accumulation in the mouse hippocampus. Our findings show that this leads to a reduction in the glutamate uptake capacity of hippocampal astrocytes, with no change in their potassium buffering ability. We find that the NMDA/AMPA ratio in CA1 pyramidal cells (CA1-PCs) is reduced in mice injected with the AAV-Aß₄₂. These data identify astrocytic glutamate uptake and NMDA/AMPA receptors as key targets of Aß₄₂ accumulation in the hippocampus, paving the way to a deeper understanding of the onset and progression of idiopathic AD.

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