title: Decreased cerebrospinal fluid levels of neurosin (KLK6), an aging-related protease, as a possible new risk factor for Alzheimer's disease.
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.
authors.affiliation: Department of Cell Biology, Research Institute for Geriatrics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Mitsui
authors.forename: Akira
authors.initials: A
authors.lastname: Okui
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Uemura
authors.forename: Toshiki
authors.initials: T
authors.lastname: Mizuno
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamada
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamamura
authors.forename: Nozomi
authors.initials: N
authors.lastname: Yamaguchi
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000453:epidemiology / Q000503:physiopathology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000134:cerebrospinal fluid*; D016631:Lewy Bodies / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C103551:KLK6 protein, human; D007610:Kallikreins