Reduced expression of amyloid precursor protein, presenilin-1 and rab3a in cortical brain regions in Alzheimer's disease

被引:24
作者
Davidsson, P [1 ]
Bogdanovic, N
Lannfelt, L
Blennow, K
机构
[1] Univ Gothenburg, Expt Neurosci Sect, Dept Clin Neurosci, SE-43180 Molndal, Sweden
[2] Huddinge Hosp, KFC Novum, Geriatr Sect, Dept Clin Neurosci & Family Med, S-14186 Huddinge, Sweden
关键词
amyloid precursor protein; Alzheimer's disease; cortical brain regions; immunoblotting; presenilin-1; rab3a;
D O I
10.1159/000051266
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
To study the role of amyloid precursor protein (APP) in the pathogenesis of Alzheimer's disease (AD), the level of APP was analysed by quantitative immunoblotting in 6 AD patients and 6 age-matched controls in 9 brain regions. These were associative cortices (orbital frontal cortex, inferior temporal cortex, inferior parietal cortex), primary cortex (occipital cortex), limbic structures (anterior cingulate gyrus, hippocampus), subcortical structures (putamen, thalamus) and cerebellum. To assess a potential relationship between APP and presenilin-1 (PS-1) and/or synaptic proteins, the levels of PS-1 and rab3a, a specific synaptic vesicle protein, were also determined in the same tissue samples. The level of APP was almost the same in the association cortical regions, primary cortex, and limbic structures and in the subcortical structures, while the lowest level was found in the cerebellum. There were more marked differences in the level of PS-1 and rab3a between different brain regions. The highest levels of PS-1 and rab3a were found in the association cortical areas, while intermediate levels were found in primary cortex, limbic structures and subcortical structures. As for APP, the lowest level was found in cerebellum. We found significantly reduced levels of all three proteins in the association cortices and in hippocampus in AD. Our data show that the protein levels are reduced in specific areas, restricted to neuronal populations that are known to degenerate in AD. Due to the similarity of the expression of APP, PS-1 and rab3a, it is tempting to speculate whether there is a functional relationship between these proteins. Copyright (C) 2001 S. Karger AG, Basel.
引用
收藏
页码:243 / 250
页数:8
相关论文
共 78 条
[51]   THE MOLECULAR PATHOGENESIS OF ALZHEIMERS-DISEASE - CLINICAL PROSPECTS [J].
MURPHY, M .
LANCET, 1992, 340 (8834-5) :1512-1515
[52]   Presenilin 1 mRNA expression in hippocampi of sporadic Alzheimer's disease patients [J].
Nishiyama, K ;
Murayama, S ;
Suzuki, T ;
Mitsui, Y ;
Sakaki, Y ;
Kanazawa, I .
NEUROSCIENCE RESEARCH, 1996, 26 (01) :75-78
[53]   ALZHEIMER-BETA-A4 AMYLOID PRECURSOR PROTEIN IN HUMAN BRAIN - AGING-ASSOCIATED INCREASES IN HOLOPROTEIN AND IN A PROTEOLYTIC FRAGMENT [J].
NORDSTEDT, C ;
GANDY, SE ;
ALAFUZOFF, I ;
CAPORASO, GL ;
IVERFELDT, K ;
GREBB, JA ;
WINBLAD, B ;
GREENGARD, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (20) :8910-8914
[54]  
OUIMET CC, 1994, J COMP NEUROL, V348, P144
[55]   AMYLOID PROTEIN-PRECURSOR MESSENGER-RNAS - DIFFERENTIAL EXPRESSION IN ALZHEIMERS-DISEASE [J].
PALMERT, MR ;
GOLDE, TE ;
COHEN, ML ;
KOVACS, DM ;
TANZI, RE ;
GUSELLA, JF ;
USIAK, MF ;
YOUNKIN, LH ;
YOUNKIN, SG .
SCIENCE, 1988, 241 (4869) :1080-1084
[56]   THE BETA-AMYLOID PROTEIN-PRECURSOR OF ALZHEIMER-DISEASE HAS SOLUBLE DERIVATIVES FOUND IN HUMAN-BRAIN AND CEREBROSPINAL-FLUID [J].
PALMERT, MR ;
PODLISNY, MB ;
WITKER, DS ;
OLTERSDORF, T ;
YOUNKIN, LH ;
SELKOE, DJ ;
YOUNKIN, SG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (16) :6338-6342
[57]   Presenilin proteins undergo heterogeneous endoproteolysis between Thr(291) and Ala(299) and occur as stable N- and C-terminal fragments in normal and Alzheimer brain tissue [J].
Podlisny, MB ;
Citron, M ;
Amarante, P ;
Sherrington, R ;
Xia, WM ;
Zhang, JM ;
Diehl, T ;
Levesque, G ;
Fraser, P ;
Haass, C ;
Koo, EHM ;
Seubert, P ;
StGeorgeHyslop, P ;
Teplow, DB ;
Selkoe, DJ .
NEUROBIOLOGY OF DISEASE, 1997, 3 (04) :325-337
[58]   INCREASE OF SYNAPTIC DENSITY AND MEMORY RETENTION BY A PEPTIDE REPRESENTING THE TROPHIC DOMAIN OF THE AMYLOID BETA/A4 PROTEIN-PRECURSOR [J].
ROCH, JM ;
MASLIAH, E ;
ROCHLEVECQ, AC ;
SUNDSMO, MP ;
OTERO, DAC ;
VEINBERGS, I ;
SAITOH, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) :7450-7454
[59]   FAMILIAL ALZHEIMERS-DISEASE IN KINDREDS WITH MISSENSE MUTATIONS IN A GENE ON CHROMOSOME-1 RELATED TO THE ALZHEIMERS-DISEASE TYPE-3 GENE [J].
ROGAEV, EI ;
SHERRINGTON, R ;
ROGAEVA, EA ;
LEVESQUE, G ;
IKEDA, M ;
LIANG, Y ;
CHI, H ;
LIN, C ;
HOLMAN, K ;
TSUDA, T ;
MAR, L ;
SORBI, S ;
NACMIAS, B ;
PIACENTINI, S ;
AMADUCCI, L ;
CHUMAKOV, I ;
COHEN, D ;
LANNFELT, L ;
FRASER, PE ;
ROMMENS, JM ;
STGEORGEHYSLOP, PH .
NATURE, 1995, 376 (6543) :775-778
[60]   AMYLOID PRECURSOR PROTEIN IS ENRICHED IN AXOLEMMA AND PERIAXOLEMMAL-MYELIN AND ASSOCIATED CLATHRIN-COATED VESICLES [J].
SAPIRSTEIN, VS ;
DURRIE, R ;
BERG, MJ ;
MARKS, N .
JOURNAL OF NEUROSCIENCE RESEARCH, 1994, 37 (03) :348-358