2009
DOI: 10.1002/ana.21623
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A γ‐secretase inhibitor decreases amyloid‐β production in the central nervous system

Abstract: Objective Accumulation of amyloid-β (Aβ) by over-production or under-clearance in the central nervous system is hypothesized to be a necessary event in the pathogenesis of Alzheimer Disease. However, previously there has not been a method to determine drug effects on Aβ production or clearance in the human central nervous system. The objective of this study was to determine the effects of a gamma-secretase inhibitor on the production of Aβ in the human CNS. Methods We utilized a recently developed method of … Show more

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Cited by 299 publications
(229 citation statements)
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References 27 publications
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“…Previous studies used labeling with 13 C 6 ‐Leucine to measure inhibition of amyloid beta peptide synthesis by a gamma secretase inhibitor in human participants 30. However, these experiments were performed over a 36‐hour time period, as the half‐life of amyloid beta peptide is ~9 h in CSF 18.…”
Section: Discussionmentioning
confidence: 99%
“…Previous studies used labeling with 13 C 6 ‐Leucine to measure inhibition of amyloid beta peptide synthesis by a gamma secretase inhibitor in human participants 30. However, these experiments were performed over a 36‐hour time period, as the half‐life of amyloid beta peptide is ~9 h in CSF 18.…”
Section: Discussionmentioning
confidence: 99%
“…Even though the mean decrease was different depending on the dose of clearance among groups remained the same. Clearly, through this SILK study the group was able to determine the amount of Ab produced and cleared successfully [29].…”
Section: Mass Spectrometrymentioning
confidence: 99%
“…This technique allows for determination of production and clearance rates of total A in CSF and plasma and may help 11 addressing the fundamental question if patients who develop AD have increased production or decreased clearance of the peptide. Its value as a diagnostic tool is unknown, but recent data show that it is very sensitive to identify biochemical effects of secretase inhibition in human subjects (Bateman et al, 2009). …”
Section: A-related Proteins As Core Neurochemical Markers Of Admentioning
confidence: 99%
“…While it is clear that A42 along with tau protein levels in CSF are useful in clinical routine (Andreasen et al, 2001;Frisoni et al, 2009) and probably also to detect biochemical effects on amyloid deposition and axonal degeneration of novel drug candidates against AD (Bateman et al, 2009;Kadir et al, 2008;Lannfelt et al, 2008), it has been difficult to find reliable amyloid biomarkers in peripheral blood (Irizarry, 2004;Zetterberg, 2008). Many studies have examined plasma levels of A in the context of sporadic AD but the findings are contradictory.…”
Section: A-related Proteins As Core Neurochemical Markers Of Admentioning
confidence: 99%