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• W2061535110 abstract "Alterations in cellular cholesterol synthesis or content in cultured neurons affect the cleavage of amyloid precursor protein to amyloidogenic Aβ 40 and Aβ 42 peptides characteristic of Alzheimer's disease. To determine whether a decrease in cholesterol synthesis affects amyloid precursor protein processing in vivo, we crossed cholesterol 24-hydroxylase knockout mice, which exhibit a 50% reduction in brain sterol synthesis, with transgenic mice [B6.Cg-Tg(APPswe, PSEN1E9)85Dbo/J] that develop Alzheimer's disease-like pathology. Amyloid precursor protein expression and amyloid plaque deposition in the cortex and hippocampus of male and female Alzheimer's disease mice between the ages of 3 to 15 months were similar in the presence and absence of cholesterol 24-hydroxylase. A modest but statistically significant decline in insoluble Aβ 42 peptide levels was detected in the hippocampus of 12-month-old knockout/Alzheimer's disease males. The levels of insoluble Aβ 40 and Aβ 42 peptides in 15-month-old knockout/Alzheimer's disease females were also reduced slightly. Although amyloid plaque accumulation did not affect brain sterol or fatty acid synthesis rates in 24-hydroxylase WT or knockout mice, loss of one or both cholesterol 24-hydroxylase alleles increased longevity in Alzheimer's disease mice. These studies suggest that reducing de novo cholesterol synthesis in the brain will not substantially alter the course of Alzheimer's disease, but may confer a survival advantage." @default.
• W2061535110 created "2016-06-24" @default.
• W2061535110 creator A5039217535 @default.
• W2061535110 creator A5047241618 @default.
• W2061535110 date "2009-03-03" @default.
• W2061535110 modified "2023-09-27" @default.
• W2061535110 title "Reduction of cholesterol synthesis in the mouse brain does not affect amyloid formation in Alzheimer's disease, but does extend lifespan" @default.
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• W2061535110 doi "https://doi.org/10.1073/pnas.0813349106" @default.
• W2061535110 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2651246" @default.
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