Levels of α- and β-secretase cleaved amyloid precursor protein in the cerebrospinal fluid of Alzheimer's disease patients

被引:159
作者
Sennvik, K
Fastbom, J
Blomberg, M
Wahlund, LO
Winblad, B
Benedikz, E [1 ]
机构
[1] Karolinska Inst, NEUROTEC, KFC NOVUM, Div Geriatr Med, S-14186 Huddinge, Sweden
[2] Huddinge Univ Hosp, S-14186 Huddinge, Sweden
关键词
amyloid precursor protein; Alzheimer's disease; cerebrospinal fluid; secretase; metabolism; Western blot;
D O I
10.1016/S0304-3940(99)00929-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Alternative cleavage of the amyloid precursor protein (APP) results in generation and secretion of both soluble APP (sAPP) and beta-amyloid (A beta). A beta is the main component of the amyloid depositions in the brains of Alzheimer's disease (AD) patients. Using Western blotting, we compared the levels of alpha-secretase cleaved sAPP, beta-secretase cleaved sAPP and total sAPP, in cerebrospinal fluid (CSF) from 13 sporadic AD patients and 13 healthy controls. Our findings show significant amounts of beta-secretase cleaved sAPP in CSF. There was no statistically significant difference in the levels of beta-secretase cleaved sAPP between AD patients and controls. The levels of alpha-secretase cleaved sAPP and total sAPP were, however, found to be significantly lower in the AD patients than in the controls. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:169 / 172
页数:4
相关论文
共 16 条
[1]   Cerebrospinal fluid levels of alpha-secretase-cleaved soluble amyloid precursor protein mirror cognition in a Swedish family with Alzheimer disease and a gene mutation [J].
Almkvist, O ;
Basun, H ;
Wagner, SL ;
Rowe, BA ;
Wahlund, LO ;
Lannfelt, L .
ARCHIVES OF NEUROLOGY, 1997, 54 (05) :641-644
[2]   Reduced cerebrospinal fluid levels of α-secretase-cleaved amyloid precursor protein in aged rats:: Correlation with spatial memory deficits [J].
Anderson, JJ ;
Holtz, G ;
Baskin, PP ;
Wang, R ;
Mazzarelli, L ;
Wagner, SL ;
Menzaghi, F .
NEUROSCIENCE, 1999, 93 (04) :1409-1420
[3]   Novel beta-secretase cleavage of beta-amyloid precursor protein in the endoplasmic reticulum intermediate compartment of NT2N cells [J].
Chyung, ASC ;
Greenberg, BD ;
Cook, DG ;
Doms, RW ;
Lee, VMY .
JOURNAL OF CELL BIOLOGY, 1997, 138 (03) :671-680
[4]   GENERATION OF AMYLOID-BETA PROTEIN FROM ITS PRECURSOR IS SEQUENCE-SPECIFIC [J].
CITRON, M ;
TEPLOW, DB ;
SELKOE, DJ .
NEURON, 1995, 14 (03) :661-670
[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]   ALZHEIMERS-DISEASE AMYLOID PRECURSOR PROTEIN IS PRESENT IN SENILE PLAQUES AND CEREBROSPINAL-FLUID - IMMUNOHISTOCHEMICAL AND BIOCHEMICAL-CHARACTERIZATION [J].
GHISO, J ;
TAGLIAVINI, F ;
TIMMERS, WF ;
FRANGIONE, B .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 163 (01) :430-437
[7]   THE SWEDISH MUTATION CAUSES EARLY-ONSET ALZHEIMERS-DISEASE BY BETA-SECRETASE CLEAVAGE WITHIN THE SECRETORY PATHWAY [J].
HAASS, C ;
LEMERE, CA ;
CAPELL, A ;
CITRON, M ;
SEUBERT, P ;
SCHENK, D ;
LANNFELT, L ;
SELKOE, DJ .
NATURE MEDICINE, 1995, 1 (12) :1291-1296
[8]   Amyloid, the presenilins and Alzheimer's disease [J].
Hardy, J .
TRENDS IN NEUROSCIENCES, 1997, 20 (04) :154-159
[9]   Membrane protein secretases [J].
Hooper, NM ;
Karran, EH ;
Turner, AJ .
BIOCHEMICAL JOURNAL, 1997, 321 :265-279
[10]   THE PRECURSOR OF ALZHEIMERS-DISEASE AMYLOID-A4 PROTEIN RESEMBLES A CELL-SURFACE RECEPTOR [J].
KANG, J ;
LEMAIRE, HG ;
UNTERBECK, A ;
SALBAUM, JM ;
MASTERS, CL ;
GRZESCHIK, KH ;
MULTHAUP, G ;
BEYREUTHER, K ;
MULLERHILL, B .
NATURE, 1987, 325 (6106) :733-736