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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents



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ID: 556522.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Genetic variants in PSEN2 and correlation to CSF beta-amyloid42 levels in AD.
Authors:Lebedeva, E.; Stingl, J. C.; Thal, D. R.; Ghebremedhin, E.; Strauss, J.; Özer, E.; Bertram, L.; von Einem, B.; Tumani, H.; Otto, M.; Riepe, M. W.; Högel, J.; Ludolph, A. C.; von Arnim, C. A.
Language:English
Date of Publication (YYYY-MM-DD):2010
Title of Journal:Neurobiology of Aging
Journal Abbrev.:Neurobiol Aging
Copyright:© 2010 Elsevier Inc. All rights reserved.
Review Status:not specified
Audience:Experts Only
Abstract / Description:Beta-amyloid 42 (Abeta42) concentrations in cerebrospinal fluid (CSF) are significantly decreased in Alzheimer's disease (AD). The aim of this study was to correlate genetic variability in presenilin 2 (PSEN2) in relation to Abeta42 concentrations and to confirm association of apolipoprotein E (APOE) alleles E4/E4 genotype with lower CSF Abeta42. Haplotype analysis of PSEN2 and APOE genotyping were performed in 175 Alzheimer's disease patients, as defined by clinical diagnosis and Abeta42 levels. One distinct haploblock in PSEN2 was detected and the frequent haplotypes were analyzed using 4 tagging single nucleotide polymorphisms (SNPs). We found an association between haplotype 2 and higher CSF Abeta42 concentrations (p = 0.021) and lower Abeta42 concentrations in haplotype 5 carriers (p < 0.001). APOE E4/E4 carriers had lower Abeta42 levels (p = 0.009). Additive regression analysis showed an association of Abeta42 level with APOE genotype (p = 0.024), haplotype 4 (p = 0.064), and haplotype 5 (p = 0.04), whereas gender, age at onset and Mini Mental State Examination (MMSE) remained insignificant. Using CSF Abeta42 as a biomarker we replicated genetic influences in APOE and observed a significant influence of a new haplotype in PSEN2. A better understanding of genetic influences on biomarkers like CSF Abeta42 might help to stratify patients and develop specific treatment strategies.
Free Keywords:Alzheimer's disease;
Presenilin2;
β-amyloid 42;
Haplotype;
Cerebrospinal fluid;
Apolipoprotein E
Comment of the Author/Creator:Email: christine.arnim@uni-ulm.de
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, Ulm, Germany;
2.Institute of Pathology, Laboratory of Neuropathology, Ulm University, Ulm, Germany;
3.Institute of Clinical Neuroanatomy, J.W. Goethe University, Frankfurt, Germany;
4.Department of Neurology, Ulm University, Ulm, Germany;
5.Department of Psychiatry II, Ulm University, Ulm, Germany;
6.Institute of Human Genetics, Ulm University, Ulm, Germany.
Identifiers:ISSN:0197-4580 [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=... [ID No:2]
DOI:10.1016/j.neurobiolaging.2010.07.017 [ID No:3]
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