Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease.
Ann M. Saunders,Warren J. Strittmatter,Donald E. Schmechel,P. St. George-Hyslop,Margaret A. Pericak-Vance,S. H. Joo,B.L. Rosi,James F. Gusella,D. R. Crapper-MacLachlan,Mark J. Alberts,Christine M. Hulette,Barbara J. Crain,Dmitry Goldgaber,A. D. Roses +13 more
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TLDR
Data support the involvement of ApoE ϵ4 in the pathogenesis of late-onset familial and sporadic AD and suggest it may operate as a susceptibility gene (risk factor) for the clinical expression of AD.Abstract:
Apolipoprotein E, type epsilon 4 allele (APOE epsilon 4), is associated with late-onset familial Alzheimer's disease (AD). There is high avidity and specific binding of amyloid beta-peptide with the protein ApoE. To test the hypothesis that late-onset familial AD may represent the clustering of sporadic AD in families large enough to be studied, we extended the analyses of APOE alleles to several series of sporadic AD patients. APOE epsilon 4 is significantly associated with a series of probable sporadic AD patients (0.36 +/- 0.042, AD, versus 0.16 +/- 0.027, controls [allele frequency estimate +/- standard error], p = 0.00031). Spouse controls did not differ from CEPH grandparent controls from the Centre d'Etude du Polymorphisme Humain (CEPH) or from literature controls. A large combined series of autopsy-documented sporadic AD patients also demonstrated highly significant association with the APOE epsilon 4 allele (0.40 +/- 0.026, p < or = 0.00001). These data support the involvement of ApoE epsilon 4 in the pathogenesis of late-onset familial and sporadic AD. ApoE isoforms may play an important role in the metabolism of beta-peptide, and APOE epsilon 4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD.read more
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Journal ArticleDOI
Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
Elizabeth H. Corder,Ann M. Saunders,Warren J. Strittmatter,Donald E. Schmechel,P. C. Gaskell,Gary W. Small,A. D. Roses,Jonathan L. Haines,Margaret A. Pericak-Vance +8 more
TL;DR: The APOE-epsilon 4 allele is associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD) in 42 families with late onset AD.
Journal ArticleDOI
Alzheimer's Disease: Genes, Proteins, and Therapy
TL;DR: Evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the beta-amyloid precursor protein by the protease called gamma-secretase has spurred progress toward novel therapeutics and provided discrete biochemical targets for drug screening and development.
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2016 Alzheimer's disease facts and figures
Journal ArticleDOI
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
R. Sherrington,Evgeny I. Rogaev,Yan Liang,Ekaterina Rogaeva,G. Levesque,M. Ikeda,H. Chi,Chih-Ping Lin,Gavin Li,K. Holman,T. Tsuda,L. Mar,J. F. Foncin,Amalia C. Bruni,Mp Montesi,Sandro Sorbi,Innocenzo Rainero,Lorenzo Pinessi,L. Nee,Ilya Chumakov,Daniel A. Pollen,A. Brookes,Philippe Sanseau,R. Polinsky,Wilma Wasco,H. A. R. Da Silva,Jonathan L. Haines,Margaret A. Pericak-Vance,Rudolph E. Tanzi,A. D. Roses,Paul E. Fraser,Johanna M. Rommens,P. St. George-Hyslop +32 more
TL;DR: A minimal cosegregating region containing the AD3 gene is defined, and at least 19 different transcripts encoded within this region corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein.
Journal ArticleDOI
Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis
Lindsay A. Farrer,L. Adrienne Cupples,Jonathan L. Haines,Bradley T. Hyman,Walter A. Kukull,Richard Mayeux,Richard H. Myers,Margaret A. Pericak-Vance,Neil Risch,Cornelia M. van Duijn +9 more
TL;DR: The APOE∈4 allele represents a major risk factor for AD in all ethnic groups studied, across all ages between 40 and 90 years, and in both men and women.
References
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Book
Molecular Cloning: A Laboratory Manual
TL;DR: Molecular Cloning has served as the foundation of technical expertise in labs worldwide for 30 years as mentioned in this paper and has been so popular, or so influential, that no other manual has been more widely used and influential.
Segregation of a missense mutation in the amyloid precursor protein gene with familial alzheimers-disease
A. Goate,M-C. Chartier-Harlin,Michael Mullan,J Brown,Fiona Crawford,Liana Fidani,L Giuffra,A. Haynes,N Irving,L James,R Mant,P. J. Newton,K Rooke,P Roques,C. Conover Talbot,Pericak-Vance Margareta A,A. Roses,Robert Williamson,Martin N. Rossor,M. J. Owen,John Hardy +20 more
TL;DR: It is demonstrated that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene that causes an amino-acid substitution close to the carboxy terminus of the β-amyloid peptide.
Journal ArticleDOI
Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI.
James E. Hixson,D. T. Vernier +1 more
TL;DR: This work has used restriction isotyping (restriction enzyme isoform genotyping) for rapid typing of common apolipoprotein E isoforms (E2, E3, E4) and distinguished each of the isoforms by a unique combination of HhaI fragment sizes that enabled unambiguous typing of all homozygotic and heterozygotic combinations.
Journal ArticleDOI
Amyloid β-peptide is produced by cultured cells during normal metabolism
Christian Haass,Michael G. Schlossmacher,Michael G. Schlossmacher,Albert Y. Hung,Carmen Vigo-Pelfrey,A Mellon,Beth L. Ostaszewski,Ivan Lieberburg,Edward H. Koo,Dale B. Schenk,David B. Teplow +10 more
TL;DR: The unexpected identification of the 4K (Mr 4,000) Aβ and a truncated form of Aβ in media from cultures of primary cells and untransfected and β-APP-transfected cell lines grown under normal conditions provide the basis for using simple cell culture systems to identify drugs that block the formation or release of A β, the primary protein constituent of the senile plaques of Alzheimer's disease.
Journal ArticleDOI
Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids
Peter Seubert,Carmen Vigo-Pelfrey,Frederick Esch,Michael K. Lee,Harry F. Dovey,Dave Davis,Sukanto Sinha,Michael Schiossmacher,Justine Whaley,Cathy Swindlehurst,Robert T. McCormack,Robert L. Wolfert,Dennis J. Selkoe,Ivan Lieberburg,Dale Schenk +14 more
TL;DR: It is demonstrated that Aβ is produced and released both in vivo and in vitro, and new opportunities for developing diagnostic tests for Alzheimer's disease and therapeutic strategies aimed at reducing the cerebral deposition of Aβ are offered.
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