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

Lebedeva, Elena, Stingl, Julia C., Thal, Dietmar R., Ghebremedhin, Estifanos, Strauss, Joachim, Özer, Esra, Bertram, Lars, von Einem, Björn, Tumani, Hayrettin, Otto, Markus, Riepe, Matthias W., Högel, Josef, Ludolph , Albert C. and von Arnim, Christine A. F. (2012) Genetic variants in PSEN2 and correlation to CSF beta-amyloid42 levels in AD. Neurobiology of Aging, 33 1: 201.e9-201.e18. doi:10.1016/j.neurobiolaging.2010.07.017

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Author Lebedeva, Elena
Stingl, Julia C.
Thal, Dietmar R.
Ghebremedhin, Estifanos
Strauss, Joachim
Özer, Esra
Bertram, Lars
von Einem, Björn
Tumani, Hayrettin
Otto, Markus
Riepe, Matthias W.
Högel, Josef
Ludolph , Albert C.
von Arnim, Christine A. F.
Title Genetic variants in PSEN2 and correlation to CSF beta-amyloid42 levels in AD
Formatted title
Genetic variants in PSEN2 and correlation to CSF β-amyloid42 levels in AD
Journal name Neurobiology of Aging   Check publisher's open access policy
ISSN 0197-4580
Publication date 2012-01-01
Year available 2010
Sub-type Article (original research)
DOI 10.1016/j.neurobiolaging.2010.07.017
Open Access Status DOI
Volume 33
Issue 1
Start page 201.e9
End page 201.e18
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
Formatted abstract
Beta-amyloid 42 (Aβ42) 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 Aβ42 concentrations and to confirm association of apolipoprotein E (APOE) alleles E4/E4 genotype with lower CSF Aβ42. Haplotype analysis of PSEN2 and APOE genotyping were performed in 175 Alzheimer's disease patients, as defined by clinical diagnosis and Aβ42 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 Aβ42 concentrations (p = 0.021) and lower Aβ42 concentrations in haplotype 5 carriers (p < 0.001). APOE E4/E4 carriers had lower Aβ42 levels (p = 0.009). Additive regression analysis showed an association of Aβ42 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 Aβ42 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 Aβ42 might help to stratify patients and develop specific treatment strategies.
Keyword Alzheimer's disease
β-amyloid 42
Cerebrospinal fluid
Apolipoprotein E
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 20 September 2010.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biomedical Sciences Publications
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Created: Tue, 16 Nov 2010, 20:03:59 EST by Dr Estifanos Ghebremedhin on behalf of School of Biomedical Sciences