Date Approved

11-24-2025

Embargo Period

11-24-2026

Document Type

Dissertation

Degree Name

Ph.D.

Department

Cell Biology and Neuroscience

College

Rowan-Virtua School of Translational Biomedical Engineering & Sciences

Advisor

Elizabeth West, Ph.D.

Committee Member 1

Jessica Loweth, Ph.D.

Committee Member 2

Daniel Chandler, Ph.D.

Committee Member 3

Rachel Navarra, Ph.D.

Committee Member 4

Travis Moschak, Ph.D.

Disciplines

Medical Sciences | Medicine and Health Sciences | Neurosciences

Abstract

Prior to the extensive accumulation of the canonical neuropathological markers of AD (β-amyloid plaques and neurofibrillary tangles), human AD patients show behavioral deficits. As AD diagnoses are expected to dramatically increase, the behavioral consequences of early-AD will rapidly become apparent and demand a thorough understanding of the disease for effective treatment prior to the devasting loss of memory. A novel rat model (Tg-F344-AD) that expresses mutant amyloid precursor protein and overexpresses presenilin-1 exhibits age-dependent AD pathology (plaques, tau pathology, and neuronal loss) and closely recapitulates the progression of human AD. These AD rats have not only deficits in flexible behavior and motivation but also alterations in the medial prefrontal cortex (mPFC) by 6 months of age. mPFC neural encoding of reward-predictive cues during learning is necessary for and can predict a rat’s ability to flexibly shift behavior. Here, using a combination of behavioral and neurophysiological techniques, we have uncovered pathological mPFC neurophysiological signatures of adult AD rats (5-7 months old) that are associated with various behavioral deficits, including flexible behavior and motivation. The work may prove invaluable to characterizing the neurophysiological signature of early disease and informing future AD therapies.

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Available for download on Tuesday, November 24, 2026

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