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Updated: Jul 5, 2026

An Improved Method for Collection of Cerebrospinal Fluid from Anesthetized Mice
Published on: March 19, 2018
Decrease in age-adjusted cerebrospinal fluid beta-secretase activity in Alzheimer's subjects
Guoxin Wu1, Sethu Sankaranarayanan, Kate Tugusheva
1Alzheimer's Research, Merck Research Laboratory, West Point, PA, USA.
Objectives:
To develop a novel cerebrospinal fluid (CSF) beta-secretase-1 activity assay and evaluate beta-secretase-1 (BACE-1) activity as a potential biomarker in human Alzheimer's disease.
Methods:
The assay consisted of an enzymatic reaction of CSF samples with an optimized beta-secretase peptide substrate and the cleavage products were detected using a neo-epitope specific antibody.
Results:
The CSF BACE-1 activity assay described exhibits time, temperature, dose, and pH dependence, with sensitivity down to <1 pM of recombinant BACE-1 enzyme, and is completely blocked by BACE-1 inhibitors. The endogenous BACE-1 enzyme in CSF appears to exist as a c-terminally truncated protein, based on both western blotting and capture-based activity assays. In a small cohort of human subjects, an age-dependent increase in CSF BACE activity was observed (~1.0 pM/year, p<0.05). In Alzheimer's disease subjects, a significant decline in age-adjusted CSF BACE activity was observed compared to controls (56% in the log-transformed scale, p=0.02).
Conclusion:
We have developed a robust assay to measure CSF BACE-1 activity which could serve as a potential biomarker in human Alzheimer's disease subjects.
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