ISOFORM-SPECIFIC INTERACTIONS OF APOLIPOPROTEIN-E WITH MICROTUBULE-ASSOCIATED PROTEIN TAN - IMPLICATIONS FOR ALZHEIMER-DISEASE

被引:435
作者
STRITTMATTER, WJ
SAUNDERS, AM
GOEDERT, M
WEISGRABER, KH
DONG, LM
JAKES, R
HUANG, DY
PERICAKVANCE, M
SCHMECHEL, D
ROSES, AD
机构
[1] DUKE UNIV,MED CTR,JOSEPH & KATHLEEN BRYAN ALZHEIMERS DIS RES CTR,DEPT NEUROBIOL,DURHAM,NC 27710
[2] MRC,MOLEC BIOL LAB,CAMBRIDGE CB2 2QH,ENGLAND
[3] UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,INST CARDIOVASC RES,DEPT PATHOL,SAN FRANCISCO,CA 94143
关键词
D O I
10.1073/pnas.91.23.11183
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
The apolipoprotein E (apoE) type 4 allele (APOE4) is a susceptibility gene for late-onset familial and sporadic Alzheimer disease. ApoE is found in some neurofibrillary tangle-bearing neurons, one of the major pathologic hallmarks of the disease. Neurofibrillary tangles contain paired helical filaments formed from hyperphosphorylated microtubule-associated protein tan. In vitro, tau binds avidly to apoE3, but not to apoE4, forming a bimolecular complex. Tau phosphorylated with a brain extract does not bind either isoform. ApoE3 binds to the microtubule-binding repeat region of tau, which is also the region that is thought to cause self assembly into the paired helical filament. Binding studies with fragments of ApoE demonstrate that the tau-binding region of apoE3 corresponds to its receptor-binding domain and is distinct from the region that binds lipoprotein particles or beta/A4 peptide. Isoform-specific interactions of apoE with tau may regulate intraneuronal tau metabolism in Alzheimer disease and alter the rate of formation of paired helical filaments and neurofibrillary tangles.
引用
收藏
页码:11183 / 11186
页数:4
相关论文
共 42 条
  • [1] NEUROFIBRILLARY TANGLES BUT NOT SENILE PLAQUES PARALLEL DURATION AND SEVERITY OF ALZHEIMERS-DISEASE
    ARRIAGADA, PV
    GROWDON, JH
    HEDLEYWHYTE, ET
    HYMAN, BT
    [J]. NEUROLOGY, 1992, 42 (03) : 631 - 639
  • [2] APOLIPOPROTEIN-E IMMUNOREACTIVE DEPOSITS IN INCLUSION-BODY MUSCLE DISEASES
    ASKANAS, V
    MIRABELLA, M
    ENGEL, WK
    ALVAREZ, RB
    WEISGRABER, KH
    [J]. LANCET, 1994, 343 (8893) : 364 - 365
  • [3] BETA-AMYLOID PRECURSOR EPITOPES IN MUSCLE-FIBERS OF INCLUSION-BODY MYOSITIS
    ASKANAS, V
    ALVAREZ, RB
    ENGEL, WK
    [J]. ANNALS OF NEUROLOGY, 1993, 34 (04) : 551 - 560
  • [4] ASKANAS V, 1994, AM J PATHOL, V144, P177
  • [5] THE SWITCH OF TAU-PROTEIN TO AN ALZHEIMER-LIKE STATE INCLUDES THE PHOSPHORYLATION OF 2 SERINE PROLINE MOTIFS UPSTREAM OF THE MICROTUBULE BINDING REGION
    BIERNAT, J
    MANDELKOW, EM
    SCHROTER, C
    LICHTENBERGKRAAG, B
    STEINER, B
    BERLING, B
    MEYER, H
    MERCKEN, M
    VANDERMEEREN, A
    GOEDERT, M
    MANDELKOW, E
    [J]. EMBO JOURNAL, 1992, 11 (04) : 1593 - 1597
  • [6] APOLIPOPROTEIN-E DEGRADATION IN HUMAN VERY LOW-DENSITY LIPOPROTEINS BY PLASMA PROTEASE(S) - CHEMICAL AND BIOLOGICAL CONSEQUENCES
    BRADLEY, WA
    GILLIAM, EB
    GOTTO, AM
    GIANTURCO, SH
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1982, 109 (04) : 1360 - 1367
  • [7] PROTECTIVE EFFECT OF APOLIPOPROTEIN-E TYPE-2 ALLELE FOR LATE-ONSET ALZHEIMER-DISEASE
    CORDER, EH
    SAUNDERS, AM
    RISCH, NJ
    STRITTMATTER, WJ
    SCHMECHEL, DE
    GASKELL, PC
    RIMMLER, JB
    LOCKE, PA
    CONNEALLY, PM
    SCHMADER, KE
    SMALL, GW
    ROSES, AD
    HAINES, JL
    PERICAKVANCE, MA
    [J]. NATURE GENETICS, 1994, 7 (02) : 180 - 184
  • [8] 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
  • [9] THE MICROTUBULE BINDING REPEATS OF TAU PROTEIN ASSEMBLE INTO FILAMENTS LIKE THOSE FOUND IN ALZHEIMERS-DISEASE
    CROWTHER, RA
    OLESEN, OF
    JAKES, R
    GOEDERT, M
    [J]. FEBS LETTERS, 1992, 309 (02) : 199 - 202
  • [10] TAU-PROTEIN AND PAIRED HELICAL FILAMENTS OF ALZHEIMERS-DISEASE
    CROWTHER, RA
    [J]. CURRENT OPINION IN STRUCTURAL BIOLOGY, 1993, 3 (02) : 202 - 206