ALLELE EPSILON-4 OF APOLIPOPROTEIN-E SHOWS A DOSE-EFFECT ON AGE AT ONSET OF PICK DISEASE

被引:47
作者
FARRER, LA
ABRAHAM, CR
VOLICER, L
FOLEY, EJ
KOWALL, NW
MCKEE, AC
WELLS, JM
机构
[1] BOSTON UNIV,SCH MED,DEPT EPIDEMIOL & BIOSTAT,BOSTON,MA 02118
[2] BOSTON UNIV,SCH MED,DEPT MED,BOSTON,MA 02118
[3] BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02118
[4] BOSTON UNIV,SCH MED,DEPT PHARMACOL,BOSTON,MA 02118
[5] EDITH NOURSE ROGERS MEM VET ADM HOSP,CTR GERIATR RES EDUC & CLIN,BEDFORD,MA 01730
关键词
D O I
10.1006/exnr.1995.1093
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Pick. disease is a rare progressive dementing illness characterized by severe atrophy of the frontal and temporal lobes. Clinically, Pick disease may be difficult to distinguish from Alzheimer disease (AD), The fact that Pick disease is often familial, and the evidence suggesting that the epsilon 4 allele of apolipoprotein E (ApoE) is a risk factor for AD and possibly other dementias, prompted us to study ApoE isoforms in Pick disease. ApoE genotypes were evaluated in an autopsy series of 21 AD and 12 Pick cases and compared with published data for a large group of adults participating in the Framingham Study. The distributions of ApoE genotypes in the AD and Pick patients and the controls were significantly different from one another, The frequency of epsilon 4 was 50.0, 20.0, and 13.6% in these respective groups. Linear regression analysis showed that the number of epsilon 4 alleles was inversely related to age at onset of Pick. disease (P < 0.03) and accounted for 40% of the variation in age at onset. These results suggest that epsilon 4 may be a susceptibility factor for dementia and not specifically for AD. Experiments using a monoclonal antibody against ApoE suggest that neurons and Pick bodies are immunoreactive with ApoE, The dose effect of the epsilon 4 allele on age at onset of dementias other than AD and the association of ApoE immunoreactivity with neurons and Pick bodies support a broader role for ApoE in the pathogenesis of neuronal degeneration through interactions with the neuronal cytoskeleton. (C) 1995 Academic Press, Inc.
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页码:162 / 170
页数:9
相关论文
共 55 条
[1]   THE APOLIPOPROTEIN-E ALLELES AS MAJOR SUSCEPTIBILITY FACTORS FOR CREUTZFELDT-JAKOB-DISEASE [J].
AMOUYEL, P ;
VIDAL, O ;
LAUNAY, JM ;
LAPLANCHE, JL .
LANCET, 1994, 344 (8933) :1315-1318
[2]   APOLIPOPROTEIN-E GENES IN LEWY BODY AND PARKINSONS-DISEASE [J].
BENJAMIN, R ;
LEAKE, A ;
EDWARDSON, JA ;
MCKEITH, IG ;
INCE, PG ;
PERRY, RH ;
MORRIS, CM .
LANCET, 1994, 343 (8912) :1565-1565
[3]   LINKAGE OF LATE-ONSET ALZHEIMERS-DISEASE WITH APOLIPOPROTEIN-E TYPE-4 ON CHROMOSOME-19 [J].
BORGAONKAR, DS ;
SCHMIDT, LC ;
MARTIN, SE ;
KANZER, MD ;
EDELSOHN, L ;
GROWDON, J ;
FARRER, LA .
LANCET, 1993, 342 (8871) :625-625
[4]   APOLIPOPROTEIN-E ASSOCIATED WITH ASTROCYTIC GLIA OF THE CENTRAL NERVOUS-SYSTEM AND WITH NONMYELINATING GLIA OF THE PERIPHERAL NERVOUS-SYSTEM [J].
BOYLES, JK ;
PITAS, RE ;
WILSON, E ;
MAHLEY, RW ;
TAYLOR, JM .
JOURNAL OF CLINICAL INVESTIGATION, 1985, 76 (04) :1501-1513
[5]  
BRUN A, 1994, J NEUROL NEUROSUR PS, V57, P416
[6]   APOLIPOPROTEIN-E, EPSILON-4 ALLELE AS A MAJOR RISK FACTOR FOR SPORADIC EARLY AND LATE-ONSET FORMS OF ALZHEIMERS-DISEASE - ANALYSIS OF THE 19Q13.2 CHROMOSOMAL REGION [J].
CHARTIERHARLIN, MC ;
PARFITT, M ;
LEGRAIN, S ;
PEREZTUR, J ;
BROUSSEAU, T ;
EVANS, A ;
BERR, C ;
VIDAL, O ;
ROQUES, P ;
GOURLET, V ;
FRUCHART, JC ;
DELACOURTE, A ;
ROSSOR, M ;
AMOUYEL, P .
HUMAN MOLECULAR GENETICS, 1994, 3 (04) :569-574
[7]  
CONSTANTINIDIS J, 1962, Encephale, V51, P301
[8]   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
[9]   MARKED CHANGES IN MITOCHONDRIAL-DNA DELETION LEVELS IN ALZHEIMER BRAINS [J].
CORRALDEBRINSKI, M ;
HORTON, T ;
LOTT, MT ;
SHOFFNER, JM ;
MCKEE, AC ;
BEAL, MF ;
GRAHAM, BH ;
WALLACE, DC .
GENOMICS, 1994, 23 (02) :471-476
[10]  
Elston RC, 1987, ESSENTIALS BIOSTATIS