Suspected limited efficacy of γ-secretase modulators.
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.
Department of Neuropathology, Faculty of Life and Medical Sciences, Doshisha University, Kizugawa, Kyoto, Japan.
Nobuto
N
Kakuda
Kohei
K
Akazawa
Hiroyuki
H
Hatsuta
Shigeo
S
Murayama
Yasuo
Y
Ihara
D000369:Aged, 80 and over; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001923:Brain Chemistry; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D053829:Amyloid Precursor Protein Secretases