Decreased Cerebrospinal Fluid Levels of Neurosin (KLK6), an Aging‐Related Protease, as a Possible New Risk Factor for Alzheimer's Disease

Annals of the New York Academy of Sciences - Tập 977 Số 1 - Trang 216-223 - 2002
Shinichi Mitsui1, Akira Okui2, Hidetoshi Uemura2, Toshiki Mizuno3, Tatsuo Yamada4, YOSHIO YAMAMURA1, Nozomi Yamaguchi1
1Department of Cell Biology, Research Institute for Geriatrics, Kyoto Prefectural University of Medicine, Kyoto 602‐8566, Japan
2Research and Development Center, Fuso Pharmaceutical Industries Limited, Osaka 536‐8523, Japan
3Department of Neurology and Gerontology, Kyoto Prefectural University of Medicine, Kyoto 602‐8566, Japan
4Department of Internal Medicine and Health Care, Fukuoka University, Hakata 814‐0180, Japan

Tóm tắt

Abstract: Neurosin is a kallikrein‐like serine protease expressed preferentially in the human brain. It is localized in senile plaques and neurofibrillary tangles in the brains of individuals with Alzheimer's disease (AD) and in Lewy bodies in patients with Parkinson's disease. Neurosin is present in the cerebrospinal fluid (CSF) as a proenzyme and does not show any enzymatic activity. We have developed a sandwich ELISA system using monoclonal and polyclonal antibodies against human neurosin and have measured neurosin levels in the CSF from AD and non‐CNS disease patients. Both male and female patients with peripheral neuropathy showed statistically positive correlations between CSF neurosin concentrations and age (males, n= 52, r= 0.482, p < 0.005; females, n= 43, r= 0.365, p < 0.005). In contrast, such positive correlation was not observed in the CSF from patients with AD. Further, some such patients showed extremely low levels of CSF neurosin. Our results suggest that neurosin is an aging‐related protease and that a decreased CSF concentration of neurosin may be a risk factor for developing AD.

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Annals of the New York Academy of Sciences

Tập 977 Số 1

216-223

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