Amyloid-beta (N3pE-42) ELISA kit

Recently, light has been shed on possible interrelations between the two most important pathological hallmarks of Alzheimer's disease (AD): the amyloid cascade and axonal degeneration. In this study, we investigated associations between s beta APP beta, a product of the cleavage of the amyloid-beta protein precursor (A beta PP) by beta-secretase, amyloid-beta 1-42 (A beta(42)), soluble SORL1 (also called LR11 or SORLA), a receptor that is involved in A beta PP processing, and the marker of axonal degeneration tau in the cerebrospinal fluid (CSF) of 76 patients with mild cognitive impairment (MCI), 61 patients with AD, and 17 patients with frontotemporal dementia, which neuropathologically is not related to the amyloid pathology. In the AD group, significant associations between sA beta PP beta, tau (p < 0.001), and soluble SORL1 (p < 0.001) were detected according to linear regression models. In patients with MCI, sA beta PP beta correlated significantly with tau (p < 0.001) and soluble SORL1 (p = 0.003). In the FTD group, only SORL1 (p = 0.011) was associated with sA beta PP beta and not tau. A beta(42) was found to be significantly related to tau levels in CSF in the MCI group (p < 0.001) and they tended to be associated in the AD group (p = 0.05). Our results provide further evidence for a link between the two facets of AD pathology, which is likely to be mediated by the binding of A beta oligomers to specifically targeted neurons, resulting in stimulating tau hyperphosphorylation and neurodegeneration.

Cholesterol has been implicated in the pathogenesis of Alzheimer's disease ( AD). Although the underlying mechanisms are not yet clear, several studies have provided evidence for the involvement of cholesterol-rich lipid rafts in the production of amyloid beta peptide (A beta), the major component of amyloid deposits in AD. In this regard, the gamma-secretase complex is responsible for the final cleavage event in the processing of beta-amyloid precursor protein (beta APP), resulting in A beta generation. The gamma-secretase complex is a multiprotein complex composed of presenilin, nicastrin (NCT), APH-1, and PEN-2. Recent reports have suggested that gamma-secretase activity is predominantly localized in lipid rafts, and presenilin and NCT have been reported to be localized in lipid rafts. In this study, various biochemical methods, including coimmunoprecipitation, in vitro gamma-secretase assay, and methyl-beta-cyclodextrin (M beta CD) treatment, are employed to demonstrate that all four components of the active endogenous gamma-secretase complex, including APH-1 and PEN-2, are associated with lipid rafts in human neuroblastoma cells (SH-SY5Y). Treatment with statins, 3-hydroxy-3- methylglutaryl-CoA-reductase inhibitors, significantly decreased the association of the beta-secretase complex with lipid rafts without affecting the distribution of flotillin-1. This effect was partially abrogated by the addition of geranylgeraniol. These results suggest that both cholesterol and protein isoprenylation influence the active gamma-secretase complex association with lipid rafts.