To date, therapies to prevent or treat Alzheimer’s disease (AD) have largely focused on removing excess aggregation-prone amyloid peptide Aβ from the brain, an approach that has produced disappointing clinical outco...To date, therapies to prevent or treat Alzheimer’s disease (AD) have largely focused on removing excess aggregation-prone amyloid peptide Aβ from the brain, an approach that has produced disappointing clinical outcomes. An alternative hypothesis proposes that Aβ production and aggregation is a symptom of a larger, systemic disease affecting the regulation of lipids, including cholesterol. In this scenario, lipid dysregulation would likely occur early in the disease process, making it an ideal target for predicting risk of mild cognitive impairment (MCI) to AD conversion. Here, we report that levels of filipin, a fluorescent polyene macrolide widely used as a diagnostic tool for diseases of lipid dysregulation, correlate with cellular damage caused by 27-hydroxycholesterol and with dementia status in human peripheral blood cells. These results provide strong preliminary data suggesting that filipin could be of use in the development of a quick and inexpensive method to measure the risk of AD conversion in patients with MCI, supplementing existing testing strategies that focus on the consequences of Aβ accumulation.展开更多
AIM: To characterize how insulin-like growth factor 2 (IGF2) mRNA binding protein p62/IMP2-2 promotes steatohepatitis in the absence of dietary cholesterol.
Cholesterol staining is a useful approach for the visualization,localization and quantification of cholesterol in cells or tissues,which is frequently used to investigate the mechanisms of some diseases such as arteri...Cholesterol staining is a useful approach for the visualization,localization and quantification of cholesterol in cells or tissues,which is frequently used to investigate the mechanisms of some diseases such as arteriosclerosis,Niemann-Pick disease type C,and Alzheimer’s disease.It can be accomplished through various microscopes including light microscope,fluorescent microscope,and electronic microscope.During the past decades,various types of methods for cholesterol staining with different principles have been established for different applications.It is important to choose an appropriate method that is suitable for particular experimental aims,features and conditions.At present,three kinds of methods are frequently applied: filipin fluorescent method,BCθ(a biotinylated and carlsberg protease-nicked derivative of perfringolysin O) toxin method,and cholesterol oxidase-diaminobenzidine(oxidase-DAB) method.Four kinds of methods are scarcely applied: Schultze method,perchloric acid-naphthoquinone method(PAN),digitonin method,and o-phthalaldehyde method.In this review,the principles,advantages,and disadvantages of these methods are compared with the emphasis of the application,sensitivity,and specificity.展开更多
文摘To date, therapies to prevent or treat Alzheimer’s disease (AD) have largely focused on removing excess aggregation-prone amyloid peptide Aβ from the brain, an approach that has produced disappointing clinical outcomes. An alternative hypothesis proposes that Aβ production and aggregation is a symptom of a larger, systemic disease affecting the regulation of lipids, including cholesterol. In this scenario, lipid dysregulation would likely occur early in the disease process, making it an ideal target for predicting risk of mild cognitive impairment (MCI) to AD conversion. Here, we report that levels of filipin, a fluorescent polyene macrolide widely used as a diagnostic tool for diseases of lipid dysregulation, correlate with cellular damage caused by 27-hydroxycholesterol and with dementia status in human peripheral blood cells. These results provide strong preliminary data suggesting that filipin could be of use in the development of a quick and inexpensive method to measure the risk of AD conversion in patients with MCI, supplementing existing testing strategies that focus on the consequences of Aβ accumulation.
基金Supported by An EASL Sheila Sherlock fellowshipa Bank Austria visiting scientist program fellowship(to Kessler SM)
文摘AIM: To characterize how insulin-like growth factor 2 (IGF2) mRNA binding protein p62/IMP2-2 promotes steatohepatitis in the absence of dietary cholesterol.
文摘Cholesterol staining is a useful approach for the visualization,localization and quantification of cholesterol in cells or tissues,which is frequently used to investigate the mechanisms of some diseases such as arteriosclerosis,Niemann-Pick disease type C,and Alzheimer’s disease.It can be accomplished through various microscopes including light microscope,fluorescent microscope,and electronic microscope.During the past decades,various types of methods for cholesterol staining with different principles have been established for different applications.It is important to choose an appropriate method that is suitable for particular experimental aims,features and conditions.At present,three kinds of methods are frequently applied: filipin fluorescent method,BCθ(a biotinylated and carlsberg protease-nicked derivative of perfringolysin O) toxin method,and cholesterol oxidase-diaminobenzidine(oxidase-DAB) method.Four kinds of methods are scarcely applied: Schultze method,perchloric acid-naphthoquinone method(PAN),digitonin method,and o-phthalaldehyde method.In this review,the principles,advantages,and disadvantages of these methods are compared with the emphasis of the application,sensitivity,and specificity.
