TY - JOUR
T1 - Developmental Perfluorooctanesulfonic acid (PFOS) exposure as a potential risk factor for late-onset Alzheimer's disease in CD-1 mice and SH-SY5Y cells
AU - Basaly, Veronia
AU - Hill, Jaunetta
AU - Bihaqi, Syed Waseem
AU - Marques, Emily
AU - Slitt, Angela L.
AU - Zawia, Nasser H.
N1 - Publisher Copyright:
© 2021
PY - 2021/9
Y1 - 2021/9
N2 - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for approximately 60–80% of dementia cases worldwide and is characterized by an accumulation of extracellular senile plaques composed of β-amyloid (Aβ) peptide and intracellular neurofibrillary tangles (NFTs) containing hyperphosphorylated tau protein. Sporadic or late-onset AD (LOAD) represents 95 % of the AD cases and its etiology does not appear to follow Mendelian laws of inheritance, thus, implicating the role of epigenetic programming and environmental factors. Apolipoprotein allele 4 (ApoE4), the only established genetic risk factor for LOAD, is suggested to accelerate 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, with potential neurotoxic effects, that poses a major threat to the ecosystem and human health. By employing in vivo and in vitro models, the present study investigated PFOS as a potential risk factor for LOAD by assessing its impact on amyloidogenesis, tau pathology, and rodent behavior. Our behavioral analysis revealed that developmentally exposed male and female mice exhibited a strong trend of increased rearing and significantly increased distance traveled in the open field test. Biochemically, GSK3β and total ApoE were increased following developmental exposure, in vivo. Furthermore, in vitro, low concentrations of PFOS elevated protein levels of APP, tau, and its site-specific phosphorylation. Differentiated SH-SY5Y cells exposed to a series of PFOS concentrations, also, had elevated protein expression of GSK3β. These data suggest that total ApoE is inducible by environmental exposure to PFOS.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for approximately 60–80% of dementia cases worldwide and is characterized by an accumulation of extracellular senile plaques composed of β-amyloid (Aβ) peptide and intracellular neurofibrillary tangles (NFTs) containing hyperphosphorylated tau protein. Sporadic or late-onset AD (LOAD) represents 95 % of the AD cases and its etiology does not appear to follow Mendelian laws of inheritance, thus, implicating the role of epigenetic programming and environmental factors. Apolipoprotein allele 4 (ApoE4), the only established genetic risk factor for LOAD, is suggested to accelerate 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, with potential neurotoxic effects, that poses a major threat to the ecosystem and human health. By employing in vivo and in vitro models, the present study investigated PFOS as a potential risk factor for LOAD by assessing its impact on amyloidogenesis, tau pathology, and rodent behavior. Our behavioral analysis revealed that developmentally exposed male and female mice exhibited a strong trend of increased rearing and significantly increased distance traveled in the open field test. Biochemically, GSK3β and total ApoE were increased following developmental exposure, in vivo. Furthermore, in vitro, low concentrations of PFOS elevated protein levels of APP, tau, and its site-specific phosphorylation. Differentiated SH-SY5Y cells exposed to a series of PFOS concentrations, also, had elevated protein expression of GSK3β. These data suggest that total ApoE is inducible by environmental exposure to PFOS.
KW - Alzheimer's disease
KW - Amyloidogenic pathway
KW - ApoE
KW - Glycogen synthase kinase-3 beta (GSK3β)
KW - PFOS
KW - Tau pathology
UR - http://www.scopus.com/inward/record.url?scp=85109154324&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2021.06.008
DO - 10.1016/j.neuro.2021.06.008
M3 - Article
C2 - 34224775
AN - SCOPUS:85109154324
SN - 0161-813X
VL - 86
SP - 26
EP - 36
JO - NeuroToxicology
JF - NeuroToxicology
ER -