Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease

被引：722

作者：

Holtzman, DM

Bales, KR

Tenkova, T

Fagan, AM

Parsadanian, M

Sartorius, LJ

Mackey, B

Olney, J

McKeel, D

Wozniak, D

Paul, SM

机构：

[1] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Ctr Study Nervous Syst Injury, St Louis, MO 63110 USA

[6] Lilly Res Labs, Neurosci Discovery Res, Indianapolis, IN 46285 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2000年 / 97卷 / 06期

关键词：

D O I：

10.1073/pnas.050004797

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：

Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (epsilon 4 > epsilon 3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-beta (A beta) peptide and its conversion to a fibrillar form. To determine the effect of apoE on A beta deposition and AD pathology, we compared App(V717F) transgenic (TG) mice expressing mouse, human, or no apoE (apoE(-/-)). A severe, plaque-associated neuritic dystrophy developed in App(V717F) TG mice expressing mouse or human apoE. Though significant levels of A beta deposition also occurred in App(V717F) TG, apoE(-/-) mice, neuritic degeneration was virtually absent, Expression of apoE3 and apoE4 in App(V717F) TG, apoE(-/-) mice resulted in fibrillar A beta deposits and neuritic plaques by 15 months of age and substantially (> 10-fold) more fibrillar deposits were observed in apoE4-expressing App(V717F) TC mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD.

引用

页码：2892 / 2897

页数：6

共 29 条

[1] Apolipoprotein E is essential for amyloid deposition in the APPV717F transgenic mouse model of Alzheimer's disease [J].

Bales, KR ;

Verina, T ;

Cummins, DJ ;

Du, YS ;

Dodel, TC ;

Saura, J ;

Fishman, CE ;

DeLong, CA ;

Piccardo, P ;

Petegnief, V ;

Ghetti, B ;

Paul, SM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (26) :15233-15238

[2] Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition [J].

Bales, KR ;

Verina, T ;

Dodel, RC ;

Du, YS ;

Altstiel, L ;

Bender, M ;

Hyslop, P ;

Johnstone, EM ;

Little, SP ;

Cummins, DJ ;

Piccardo, P ;

Ghetti, B ;

Paul, SM .

NATURE GENETICS, 1997, 17 (03) :263-264

[3] FIBRILLOGENESIS IN ALZHEIMERS-DISEASE OF AMYLOID-BETA PEPTIDES AND APOLIPOPROTEIN-E [J].

CASTANO, EM ;

PRELLI, F ;

WISNIEWSKI, T ;

GOLABEK, A ;

KUMAR, RA ;

SOTO, C ;

FRANGIONE, B .

BIOCHEMICAL JOURNAL, 1995, 306 :599-604

[4] SP-40,40 IS A CONSTITUENT OF ALZHEIMERS AMYLOID [J].

CHOIMIURA, NH ;

IHARA, Y ;

FUKUCHI, K ;

TAKEDA, M ;

NAKANO, Y ;

TOBE, T ;

TOMITA, M .

ACTA NEUROPATHOLOGICA, 1992, 83 (03) :260-264

[5] Behavioral disturbances in transgenic mice overexpressing the V717F β-amyloid precursor protein [J].

Dodart, JC ;

Meziane, H ;

Mathis, C ;

Bales, KR ;

Paul, SM ;

Ungerer, A .

BEHAVIORAL NEUROSCIENCE, 1999, 113 (05) :982-990

[6]

Du YS, 1997, J NEUROCHEM, V69, P299

[7] Unique lipoproteins secreted by primary astrocytes from wild type, apoE (-/-), and human apoE transgenic mice [J].

Fagan, AM ;

Holtzman, DM ;

Munson, G ;

Mathur, T ;

Schneider, D ;

Chang, LK ;

Getz, GS ;

Reardon, CA ;

Lukens, J ;

Shah, JA ;

LaDu, MJ .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (42) :30001-30007

[8] ALZHEIMER-TYPE NEUROPATHOLOGY IN TRANSGENIC MICE OVEREXPRESSING V717F BETA-AMYLOID PRECURSOR PROTEIN [J].

GAMES, D ;

ADAMS, D ;

ALESSANDRINI, R ;

BARBOUR, R ;

BERTHELETTE, P ;

BLACKWELL, C ;

CARR, T ;

CLEMENS, J ;

DONALDSON, T ;

GILLESPIE, F ;

GUIDO, T ;

HAGOPIAN, S ;

JOHNSONWOOD, K ;

KHAN, K ;

LEE, M ;

LEIBOWITZ, P ;

LIEBERBURG, I ;

LITTLE, S ;

MASLIAH, E ;

MCCONLOGUE, L ;

MONTOYAZAVALA, M ;

MUCKE, L ;

PAGANINI, L ;

PENNIMAN, E ;

POWER, M ;

SCHENK, D ;

SEUBERT, P ;

SNYDER, B ;

SORIANO, F ;

TAN, H ;

VITALE, J ;

WADSWORTH, S ;

WOLOZIN, B ;

ZHAO, J .

NATURE, 1995, 373 (6514) :523-527

[9] SEQUESTRATION OF AMYLOID BETA-PEPTIDE [J].

GOLDGABER, D ;

SCHWARZMAN, AI ;

BHASIN, R ;

GREGORI, L ;

SCHMECHEL, D ;

SAUNDERS, AM ;

ROSES, AD ;

STRITTMATTER, WJ .

ALZHEIMERS DISEASE: AMYLOID PRECUSOR PROTEINS, SIGNAL TRANSDUCTION, AND NEURONAL TRANSPLANTATION, 1993, 695 :139-143

[10] Expression of human apolipoprotein E reduces amyloid-β deposition in a mouse model of Alzheimer's disease [J].

Holtzman, DM ;

Bales, KR ;

Wu, S ;

Bhat, P ;

Parsadanian, M ;

Fagan, AM ;

Chang, LK ;

Sun, YL ;

Paul, SM .

JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (06) :R15-R21

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