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• W2017196579 abstract "Elevated levels of circulating cholesterol are extrinsic factors contributing to the pathogenesis of sporadic Alzheimer's disease (AD). We showed previously that rabbits fed a cholesterol-enriched diet exhibited blood-brain barrier (BBB) dysfunction, increased accumulation of apolipoprotein B (ApoB) in brain neurons, and endolysosomes in brain had disturbed structures and functions. These effects were linked to increased amyloid beta (Aβ) production, increased tau-pathology, and disrupted synaptic integrity. Because pathological changes to endolysosomes represent a very early event in sporadic AD, we determined here the extent to which ApoB-containing LDL cholesterol altered the structure and function of endolysosomes and contributed to the development of AD-like pathology in primary cultured neurons.Cholesterol distribution and endolysosome morphology were determined histologically. Endolysosome pH was measured ratio-metrically with LysoSensor dye. Endolysosome enzyme activity was measured for acid phosphatase, cathepsins B and D, and beta-site APP cleaving enzyme 1 (BACE-1). AD-like pathologies, including increased production of Aβ, increased tau-pathology, and disrupted synaptic integrity were determined using ELISA, immunoblotting, and immunostaining techniques.Treatment of neurons with ApoB-containing LDL cholesterol increased endolysosome accumulation of cholesterol, enlarged endolysosomes, and elevated endolysosome pH. In addition, ApoB-containing LDL cholesterol increased endolysosome accumulation of BACE-1, enhanced BACE-1 activity, increased Aβ levels, increased levels of phosphorylated tau, and decreased levels of synaptophysin.Our findings suggest strongly that alterations in the structure and function of endolysosomes play a key role in the exhibition of pathological features of AD that result from neuronal exposure to ApoB-containing LDL cholesterol." @default.
• W2017196579 created "2016-06-24" @default.
• W2017196579 creator A5012132969 @default.
• W2017196579 creator A5068269611 @default.
• W2017196579 creator A5074631924 @default.
• W2017196579 date "2012-12-01" @default.
• W2017196579 modified "2023-10-18" @default.
• W2017196579 title "Endolysosome involvement in LDL cholesterol-induced Alzheimer's disease-like pathology in primary cultured neurons" @default.
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• W2017196579 doi "https://doi.org/10.1016/j.lfs.2012.04.039" @default.
• W2017196579 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3431446" @default.
• W2017196579 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22580286" @default.
• W2017196579 hasPublicationYear "2012" @default.
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