Suspected limited efficacy of γ-secretase modulators.

Nobuto Kakuda, Kohei Akazawa, Hiroyuki Hatsuta, Shigeo Murayama, Yasuo Ihara, Japanese Alzheimer's Disease Neuroimaging Initiative

Department of Neuropathology, Faculty of Life and Medical Sciences, Doshisha University, Kizugawa, Kyoto, Japan.

Neurobiology of aging 2013 Apr

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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. Copyright © 2013 Elsevier Inc. All rights reserved.

Citation

Nobuto Kakuda, Kohei Akazawa, Hiroyuki Hatsuta, Shigeo Murayama, Yasuo Ihara, Japanese Alzheimer's Disease Neuroimaging Initiative. Suspected limited efficacy of γ-secretase modulators. Neurobiology of aging. 2013 Apr;34(4):1101-4