Author ORCID Identifier

https://orcid.org/0009-0008-7317-6564

Date of Graduation

5-2026

Document Type

Thesis (MS)

Program Affiliation

Neuroscience

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

Rodrigo Morales

Committee Member

Wei Cao

Committee Member

Anjali Chauhan

Committee Member

Sonia Villapol

Committee Member

Paul Schulz

Abstract

Alzheimer’s disease (AD) is the most common type of dementia. The complexity of AD is reflected in the multiple factors that can contribute to preventing or promoting the biological drivers of AD, namely amyloid-beta (Aβ) aggregation, tau deposition in the brain, and neuroinflammation. While the unmodifiable risk factor of aging is the most relevant one to increase the risk of dementia, several factors can be modified to reduce the incidence of AD. Vaccines are commonly used to protect against bacterial and viral pathogens. Recent reports suggest that immunizations can protect the brain against diverse insults, including those linked with dementia. However, comparative studies assessing the protective role of different immunization types against Alzheimer’s disease (AD) using in vivo models under similar conditions have not been conducted. On top of that, epidemiological data indicate that vaccine technologies may be relevant in reducing the risk of AD. This thesis explored the role of different vaccines technologies targeting microorganisms that affect the respiratory system to evaluate their effect in the progression of amyloid and neuroinflammatory pathologies. iv Lipopolysaccharide (LPS) injections and immunizations against coronavirus disease 19 (COVID-19), influenza and pneumonia, were administered to APP/PS1 mice modelling brain amyloidosis characteristic of AD. Cognitive and pathological features were evaluated and compared with control mice treated with phosphate-buffered saline (PBS). As expected, immunizations and LPS administrations induced inflammatory changes in peripheral compartments. Interestingly, vaccinations against COVID-19 and influenza induced specific inflammatory profiles in the brain that were linked to improved cognitive properties and amelioration of pathology compared with controls and mice immunized against pneumococcus. These findings support clinical evidence suggesting that anti-microbial vaccinations protect the brain from neurodegenerative insults. Importantly, this thesis demonstrates the neuroprotective effects of vaccinations against COVID-19.

Keywords

Alzheimer's disease, anti-microbial vaccines, prevention, mouse model, amyloid-beta, neuroinflammation

Available for download on Friday, April 09, 2027

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