Date of Award
Master of Science in Pharmaceutical Sciences
Pharmacology and Toxicology
Biomedical and Pharmaceutical Sciences
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that accounts for about 60 to 80% of dementia cases worldwide. AD is characterized by two important physiological features: extracellular senile plaques consisting of β-amyloid (Aβ) peptide that is cleaved from a larger protein called the amyloid precursor protein (APP), and intracellular neurofibrillary tangles (NFTs) containing hyperphosphorylated tau protein. The pathogenesis of sporadic or late-onset AD (LOAD) which represents 95% of the cases appears to not be heritable and may be related to epigenetic programming and environmental factors acquired earlier in life. Apolipoprotein allele 4 (ApoE4) protein is encoded by the ApoE gene and is considered the only established genetic risk factor for LOAD. It is suggested that ApoE4 affects the pathogenesis of AD by increasing tau hyperphosphorylation, inhibiting the clearance of amyloid-β (Aβ), and promoting Aβ aggregation. Perfluorooctanesulfonic acid (PFOS) is a persistent organic pollutant known to cause neurotoxicity and poses a major threat to the ecosystem and human health. The aim of this study was to investigate PFOS as a potential risk factor for LOAD by assessing the potential mechanism and impact of PFOS on three major AD-associated pathways: amyloidogenesis, tau pathology, and ApoE using in vivo and in vitro models. Our findings demonstrated that SH-SY5Y neuroblastoma cells exposed to low concentrations of PFOS showed increased protein levels of APP, tau, and phosphorylated tau (p-tau) at Ser-404 and Thr-181 sites. PFOS exposure also caused an elevation in the kinase GSK3β, ApoE4 protein levels in vitro; however, only GSK3β and ApoE were modulated in vivo. These data suggest that ApoE4 is inducible by environmental exposure to PFOS and may play a role in AD pathogenesis primarily by modulating the tau pathway via a mechanism that involves GSK3β.
Basaly, Veronia, "PERFLUOROOCTANESULFONIC ACID (PFOS) AS A POTENTIAL RISK FACTOR FOR LATE-ONSET ALZHEIMER’S DISEASE" (2020). Open Access Master's Theses. Paper 1877.