Genetic variants in PSEN2 and correlation to CSF β-amyloid42 levels in AD

NEUROBIOLOGY OF AGING

卷:33

Article

Lebedeva, Elena¹  Stingl, Julia C.¹  Thal, Dietmar R.²  Ghebremedhin, Estifanos^2,3  Strauss, Joachim¹  Oezer, Esra¹  Bertram, Lars⁴  von Einem, Bjoern⁵  Tumani, Hayrettin⁵  Otto, Markus⁵  Riepe, Matthias W.⁶  Hoegel, Josef⁷  Ludolph, Albert C.⁵  von Arnim, Christine A. F.⁵ 

[1] Univ Ulm, Inst Pharmacol Nat Prod & Clin Pharmacol, Ulm, Germany

[2] Univ Ulm, Inst Pathol, Neuropathol Lab, Ulm, Germany

[3] Goethe Univ Frankfurt, Inst Clin Neuroanat, Frankfurt, Germany

[4] Max Planck Inst Mol Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany

[5] Univ Ulm, Dept Neurol, D-7900 Ulm, Germany

[6] Univ Ulm, Dept Psychiat 2, Ulm, Germany

[7] Univ Ulm, Inst Human Genet, Ulm, Germany

关键词: Alzheimer's disease;    Presenilin2;    beta-amyloid 42;    Haplotype;    Cerebrospinal fluid;    Apolipoprotein E;   

DOI  :  10.1016/j.neurobiolaging.2010.07.017

来源: Elsevier

【 摘 要 】

Beta-amyloid 42 (A beta 42) 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 A beta 42 concentrations and to confirm association of apolipoprotein E (APOE) alleles E4/E4 genotype with lower CSF A beta 42. Haplotype analysis of PSEN2 and APOE genotyping were performed in 175 Alzheimer's disease patients, as defined by clinical diagnosis and A beta 42 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 A beta 42 concentrations (p = 0.021) and lower A beta 42 concentrations in haplotype 5 carriers (p < 0.001). APOE E4/E4 carriers had lower A beta 42 levels (p = 0.009). Additive regression analysis showed an association of A beta 42 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 A beta 42 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 A beta 42 might help to stratify patients and develop specific treatment strategies. (C) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

Free