Cerebrospinal fluid S100B is elevated in the earlier stages of Alzheimer's disease

被引:160
作者
Peskind, ER
Griffin, WST
Akama, KT
Raskind, MA
Van Eldik, LJ
机构
[1] Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA
[2] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA
[3] VA Med Ctr, Ctr Geriatr Res Educ & Clin, Little Rock, AR 72205 USA
[4] Northwestern Univ, Sch Med, Inst Neurosci, Dept Mol & Cell Biol, Chicago, IL 60611 USA
[5] NW Drug Doscovery Program, Chicago, IL 60611 USA
关键词
cerebrospinal fluid S100B; elevated; earlier stages; Alzheimer's disease;
D O I
10.1016/S0197-0186(01)00048-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Postmortem demonstration of increased expression of biologically active S100B in Alzheimer's disease (AD) and its relation to progression of neuropathological changes across the cortical regions suggests involvement of this astrocytic cytokine in the pathophysiology of AD. The hypothesis that the overexpression of S100B in Alzheimer brain is related to the progression of clinical symptoms was addressed in living persons by measuring S100B concentrations in cerebrospinal fluid (CSF) from AD patients with a broad range of clinical dementia severity and from healthy older persons. The effect of normal aging on CSF S100B concentrations also was estimated. CSF S100B did not differ between all 68 AD subjects (0.98 +/- 0.09 ng/ml (mean +/- S.E.M.)) and 25 healthy older subjects (0.81 +/- 0.13 ng/ml). When AD subjects were divided into mild/moderate stage and advanced stage clinical dementia severity by the established Clinical Dementia Rating Scale (CDR) criteria, S100B was significantly higher in the 46 mild/moderate stage AD subjects (1.17 +/-0.11 ng/ml) than in either the 22 advanced stage AD subjects (0.60 +/- 0.12 ng/ml) or the healthy older subjects. Consistent with higher CSF S100B in mild to moderate AD, there was a significant correlation among all AD subjects between CSF S100B and cognitive status as measured by the Mini Mental State Exam (MMSE) score. CSF S100B did not differ between healthy older subjects and healthy young subjects. These results suggest increased CNS expression of S100B in the earlier stages of AD, and are consistent with a role for S100B in the initiation and/or facilitation of neuritic plaque formation in AD brain. (C) 2001 Published by Elsevier Science Ltd.
引用
收藏
页码:409 / 413
页数:5
相关论文
共 40 条
[1]   Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E [J].
Barger, SW ;
Harmon, AD .
NATURE, 1997, 388 (6645) :878-881
[2]   S100-BETA PROTECTS HIPPOCAMPAL-NEURONS FROM DAMAGE-INDUCED BY GLUCOSE DEPRIVATION [J].
BARGER, SW ;
VANELDIK, LJ ;
MATTSON, MP .
BRAIN RESEARCH, 1995, 677 (01) :167-170
[3]   DISULFIDE-LINKED S100-BETA DIMERS AND SIGNAL TRANSDUCTION [J].
BARGER, SW ;
WOLCHOK, SR ;
VANELDIK, LJ .
BIOCHIMICA ET BIOPHYSICA ACTA, 1992, 1160 (01) :105-112
[4]   Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type [J].
Donato, R .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1999, 1450 (03) :191-231
[5]   MINI-MENTAL STATE - PRACTICAL METHOD FOR GRADING COGNITIVE STATE OF PATIENTS FOR CLINICIAN [J].
FOLSTEIN, MF ;
FOLSTEIN, SE ;
MCHUGH, PR .
JOURNAL OF PSYCHIATRIC RESEARCH, 1975, 12 (03) :189-198
[6]   OVEREXPRESSION OF A CALCIUM-BINDING PROTEIN, S100-BETA, IN ASTROCYTES ALTERS SYNAPTIC PLASTICITY AND IMPAIRS SPATIAL-LEARNING IN TRANSGENIC MICE [J].
GERLAI, R ;
WOJTOWICZ, JM ;
MARKS, A ;
RODER, J .
LEARNING & MEMORY, 1995, 2 (01) :26-39
[7]   Increased S100 beta in the cerebrospinal fluid of patients with frontotemporal dementia [J].
Green, AJE ;
Harvey, RJ ;
Thompson, EJ ;
Rossor, MN .
NEUROSCIENCE LETTERS, 1997, 235 (1-2) :5-8
[8]   A specific and sensitive ELISA for measuring S-100b in cerebrospinal fluid [J].
Green, AJE ;
Keir, G ;
Thompson, EJ .
JOURNAL OF IMMUNOLOGICAL METHODS, 1997, 205 (01) :35-41
[9]   Life-long overexpression of S100β in Down's syndrome:: Implications for Alzheimer pathogenesis [J].
Griffin, WST ;
Sheng, JG ;
McKenzie, JE ;
Royston, MC ;
Gentleman, SM ;
Brumback, RA ;
Cork, LC ;
Del Bigio, MR ;
Roberts, GW ;
Mrak, RE .
NEUROBIOLOGY OF AGING, 1998, 19 (05) :401-405
[10]  
GRIFFIN WST, 1989, P NATL ACAD SCI USA, V86, P7611