INCREASED AMYLOID BETA-PEPTIDE DEPOSITION IN CEREBRAL-CORTEX AS A CONSEQUENCE OF APOLIPOPROTEIN-E GENOTYPE IN LATE-ONSET ALZHEIMER-DISEASE

被引:1382
作者
SCHMECHEL, DE
SAUNDERS, AM
STRITTMATTER, WJ
CRAIN, BJ
HULETTE, CM
JOO, SH
PERICAKVANCE, MA
GOLDGABER, D
ROSES, AD
机构
[1] DUKE UNIV,MED CTR,JOSEPH & KATHLEEN BRYAN ALZHEIMERS DIS RES CTR,DURHAM,NC 27710
[2] SUNY STONY BROOK,DEPT PSYCHIAT,STONY BROOK,NY 11794
[3] VET ADM MED CTR,DURHAM,NC 27705
[4] DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710
[5] DUKE UNIV,MED CTR,DEPT NEUROBIOL,DURHAM,NC 27710
关键词
PHENOTYPE; APOE4; GENE;
D O I
10.1073/pnas.90.20.9649
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Amyloid beta-peptide (Abeta) deposition in senile plaques and cerebral vessels is a neuropathological feature of Alzheimer disease (AD). We examined the possibility that commonly observed variability in Abeta deposition in late-onset AD might be related to apolipoprotein E genotype (APOE gene; the two most common alleles are 3 and 4), since APOE4 is a susceptibility gene for late-onset AD and apolipoprotein E interacts strongly with Abeta in vitro. In an autopsy series of brains of late-onset AD patients, we found a strong association of APOE4 allele with increased vascular and plaque Abeta deposits. Late-onset AD patients with one or two APOE4 alleles have a distinct neuropathological phenotype compared with patients homozygous for APOE3.
引用
收藏
页码:9649 / 9653
页数:5
相关论文
共 39 条
[1]   MONOCLONAL-ANTIBODIES RAISED AGAINST A SUBSEQUENCE OF SENILE PLAQUE CORE PROTEIN REACT WITH PLAQUE CORES, PLAQUE PERIPHERY AND CEREBROVASCULAR AMYLOID IN ALZHEIMERS-DISEASE [J].
ALLSOP, D ;
LANDON, M ;
KIDD, M ;
LOWE, JS ;
REYNOLDS, GP ;
GARDNER, A .
NEUROSCIENCE LETTERS, 1986, 68 (02) :252-256
[2]   EARLY-ONSET ALZHEIMERS-DISEASE CAUSED BY MUTATIONS AT CODON-717 OF THE BETA-AMYLOID PRECURSOR PROTEIN GENE [J].
CHARTIERHARLIN, MC ;
CRAWFORD, F ;
HOULDEN, H ;
WARREN, A ;
HUGHES, D ;
FIDANI, L ;
GOATE, A ;
ROSSOR, M ;
ROQUES, P ;
HARDY, J ;
MULLAN, M .
NATURE, 1991, 353 (6347) :844-846
[3]   GENE DOSE OF APOLIPOPROTEIN-E TYPE-4 ALLELE AND THE RISK OF ALZHEIMERS-DISEASE IN LATE-ONSET FAMILIES [J].
CORDER, EH ;
SAUNDERS, AM ;
STRITTMATTER, WJ ;
SCHMECHEL, DE ;
GASKELL, PC ;
SMALL, GW ;
ROSES, AD ;
HAINES, JL ;
PERICAKVANCE, MA .
SCIENCE, 1993, 261 (5123) :921-923
[4]   SYNAPSE LOSS IN FRONTAL-CORTEX BIOPSIES IN ALZHEIMERS-DISEASE - CORRELATION WITH COGNITIVE SEVERITY [J].
DEKOSKY, ST ;
SCHEFF, SW .
ANNALS OF NEUROLOGY, 1990, 27 (05) :457-464
[5]   NEUROPATHOLOGICAL CHANGES IN SCRAPIE AND ALZHEIMERS-DISEASE ARE ASSOCIATED WITH INCREASED EXPRESSION OF APOLIPOPROTEIN-E AND CATHEPSIN-D IN ASTROCYTES [J].
DIEDRICH, JF ;
MINNIGAN, H ;
CARP, RI ;
WHITAKER, JN ;
RACE, R ;
FREY, W ;
HAASE, AT .
JOURNAL OF VIROLOGY, 1991, 65 (09) :4759-4768
[6]   MACROPHAGE APOLIPOPROTEIN SYNTHESIS AND ENDONEURIAL DISTRIBUTION AS A RESPONSE TO SEGMENTAL DEMYELINATION [J].
GELMAN, BB ;
GOODRUM, J ;
BOULDIN, TW .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1991, 50 (04) :383-407
[7]  
GLENNER GG, 1981, ANN PATHOL, V1, P105
[8]   SEGREGATION OF A MISSENSE MUTATION IN THE AMYLOID PRECURSOR PROTEIN GENE WITH FAMILIAL ALZHEIMERS-DISEASE [J].
GOATE, A ;
CHARTIERHARLIN, MC ;
MULLAN, M ;
BROWN, J ;
CRAWFORD, F ;
FIDANI, L ;
GIUFFRA, L ;
HAYNES, A ;
IRVING, N ;
JAMES, L ;
MANT, R ;
NEWTON, P ;
ROOKE, K ;
ROQUES, P ;
TALBOT, C ;
PERICAKVANCE, M ;
ROSES, A ;
WILLIAMSON, R ;
ROSSOR, M ;
OWEN, M ;
HARDY, J .
NATURE, 1991, 349 (6311) :704-706
[9]   CHARACTERIZATION AND CHROMOSOMAL LOCALIZATION OF A CDNA-ENCODING BRAIN AMYLOID OF ALZHEIMERS-DISEASE [J].
GOLDGABER, D ;
LERMAN, MI ;
MCBRIDE, OW ;
SAFFIOTTI, U ;
GAJDUSEK, DC .
SCIENCE, 1987, 235 (4791) :877-880
[10]   PRESENILE-DEMENTIA AND CEREBRAL-HEMORRHAGE LINKED TO A MUTATION AT CODON-692 OF THE BETA-AMYLOID PRECURSOR PROTEIN GENE [J].
HENDRIKS, L ;
VANDUIJN, CM ;
CRAS, P ;
CRUTS, M ;
VANHUL, W ;
VANHARSKAMP, F ;
WARREN, A ;
MCINNIS, MG ;
ANTONARAKIS, SE ;
MARTIN, JJ ;
HOFMAN, A ;
VAN BROECKHOVEN, C .
NATURE GENETICS, 1992, 1 (03) :218-221