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Decreased Cerebrospinal Fluid Levels of Neurosin (KLK6), an Aging‐Related Protease, as a Possible New Risk Factor for Alzheimer's Disease
Author(s) -
MITSUI SHINICHI,
OKUI AKIRA,
UEMURA HIDETOSHI,
MIZUNO TOSHIKI,
YAMADA TATSUO,
YAMAMURA YOSHIO,
YAMAGUCHI NOZOMI
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb04818.x
Subject(s) - cerebrospinal fluid , senile plaques , medicine , risk factor , endocrinology , protease , kallikrein , disease , degenerative disease , alzheimer's disease , pathology , enzyme , chemistry , biochemistry
A bstract : 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.