Author ORCID Identifier
0000-0002-9963-6310
Date of Graduation
8-2024
Document Type
Dissertation (PhD)
Program Affiliation
Neuroscience
Degree Name
Doctor of Philosophy (PhD)
Advisor/Committee Chair
Rodrigo Morales, PhD
Committee Member
Kevin A. Morano, PhD
Committee Member
Cameron Jeter, PhD
Committee Member
Rodrigo Hasbun, MD, MPH
Committee Member
Jaroslaw Aronowski, MD, PhD
Abstract
Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and predominantly affects elderly populations. This disease is well known for its effects on the brain, but a wealth of clinical reports show that dementia can also modify, or be modified by, various peripheral and systemic processes. Yet, the pathological contribution of peripheral comorbidities to AD remains to be fully understood. In an attempt to address some knowledge gaps, we characterized the cerebral and peripheral pathology in mice with history of either liver injury or sepsis. In the former subjects, we found that even in the absence of genetic risk factors for AD, elderly mice submitted to recurrent hepatotoxicity since an adult age display memory impairment congruent with persistent, but not robust deleterious changes to AD-relevant regulators in the brain and periphery. In another study, our evaluation of septic AD mice revealed a worsened progression and severity of cognitive decline, neuropathology, and various gut-brain axis modulators. Altogether, this dissertation work crucially advances knowledge of two seldom examined potential risk factors for AD.
Keywords
Acetaminophen (APAP), Liver toxicity, Elderly, Astrocytes, Microglia, Sepsis, Alzheimer's disease (AD), Amyloid beta, Amyloids, Plaques