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

被引:1369
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
    ALLSOP, D
    LANDON, M
    KIDD, M
    LOWE, JS
    REYNOLDS, GP
    GARDNER, A
    [J]. 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
    CHARTIERHARLIN, MC
    CRAWFORD, F
    HOULDEN, H
    WARREN, A
    HUGHES, D
    FIDANI, L
    GOATE, A
    ROSSOR, M
    ROQUES, P
    HARDY, J
    MULLAN, M
    [J]. 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
    CORDER, EH
    SAUNDERS, AM
    STRITTMATTER, WJ
    SCHMECHEL, DE
    GASKELL, PC
    SMALL, GW
    ROSES, AD
    HAINES, JL
    PERICAKVANCE, MA
    [J]. SCIENCE, 1993, 261 (5123) : 921 - 923
  • [4] SYNAPSE LOSS IN FRONTAL-CORTEX BIOPSIES IN ALZHEIMERS-DISEASE - CORRELATION WITH COGNITIVE SEVERITY
    DEKOSKY, ST
    SCHEFF, SW
    [J]. 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
    DIEDRICH, JF
    MINNIGAN, H
    CARP, RI
    WHITAKER, JN
    RACE, R
    FREY, W
    HAASE, AT
    [J]. JOURNAL OF VIROLOGY, 1991, 65 (09) : 4759 - 4768
  • [6] MACROPHAGE APOLIPOPROTEIN SYNTHESIS AND ENDONEURIAL DISTRIBUTION AS A RESPONSE TO SEGMENTAL DEMYELINATION
    GELMAN, BB
    GOODRUM, J
    BOULDIN, TW
    [J]. 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
    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
    [J]. NATURE, 1991, 349 (6311) : 704 - 706
  • [9] CHARACTERIZATION AND CHROMOSOMAL LOCALIZATION OF A CDNA-ENCODING BRAIN AMYLOID OF ALZHEIMERS-DISEASE
    GOLDGABER, D
    LERMAN, MI
    MCBRIDE, OW
    SAFFIOTTI, U
    GAJDUSEK, DC
    [J]. 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
    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
    [J]. NATURE GENETICS, 1992, 1 (03) : 218 - 221