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Updated: May 17, 2026

Quantitative Measurement of γ-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms
Published on: January 25, 2018
Suspected limited efficacy of γ-secretase modulators
Nobuto Kakuda1, Kohei Akazawa, Hiroyuki Hatsuta
1Department of Neuropathology, Faculty of Life and Medical Sciences, Doshisha University, Kizugawa, Kyoto, Japan.
Abstract:
Mild cognitive impairment and Alzheimer's disease (AD) are associated with changes in γ-secretase activity in the brain, producing an amyloid β-protein-42-lowering γ-modulator-like effect. We show here that this modulation occurs at the stage of amyloid deposition, presumably decades earlier than the onset of AD. In addition, γ-secretase modulator-1, a γ-modulator, altered γ-secretase activity in the AD brain but to a lesser extent than in the normal brain. These findings suggest that γ-modulators have limited efficacy against amyloid deposition and AD.
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