Influence of SORL1 gene variants:: Association with CSF amyloid-β products in probable Alzheimer's disease

被引：34

作者：

Koelsch, Heike ^{[1
]}

Jessen, Frank ^{[1
]}

Wiltfang, Jens ^{[2
]}

Lewczuk, Piotr ^{[2
]}

Dichgans, Martin ^{[3
]}

Kornhuber, Johannes ^{[2
]}

Froelich, Lutz ^{[4
]}

Heuser, Isabella ^{[5
]}

Peters, Oliver ^{[5
]}

Schulz, Joerg B. ^{[6
,7
]}

Schwab, Sibylle G. ^{[8
,9
,10
,11
]}

Maier, Wolfgang ^{[1
]}

机构：

[1] Univ Bonn, Dept Psychiat, D-53105 Bonn, Germany

[2] Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, D-8520 Erlangen, Germany

[3] Univ Munich, Dept Psychiat, D-8000 Munich, Germany

[4] Cent Inst Mental Hlth, D-6800 Mannheim, Germany

[5] Charite Univ Med Berlin, Dept Psychiat, D-13353 Berlin, Germany

[6] Univ Gottingen, Dept Neurodegenerat, D-3400 Gottingen, Germany

[7] Univ Gottingen, Restorat Res Ctr Neurol Med, D-3400 Gottingen, Germany

[8] Univ Western Australia, Med Res Ctr, Nedlands, WA 6009, Australia

[9] Univ Western Australia, Western Australian Inst Med Res, Nedlands, WA 6009, Australia

[10] Univ Western Australia, Sch Psychiat & Clin Neurosci, Nedlands, WA 6009, Australia

[11] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia

来源：

NEUROSCIENCE LETTERS | 2008年 / 440卷 / 01期

关键词：

Alzheimer dementia; SORL1; association; amyloid-beta; CSF;

D O I：

10.1016/j.neulet.2008.05.049

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

SORL1 gene variants were described as risk factors of Alzheimer's disease (AD). We investigated the association of four SORL1 variants with CSF levels of A beta(42) and A beta(40) in 153 AD patients recruited from a multicenter study of the German Competence Net Dementias. Only one SORL1 SNP was associated with altered A beta(42) levels in the single marker analysis (SNP21: p = 0.011), the other SNPs did not show an association with A beta(42) orA beta(40) CSF levels. Haplotype analysis identified a three marker SORL1 haplotype consisting of SNP19 T-allele, SNP21 G-allele and SNP23 A-allele (T/G/A) which was associated with reduced A beta(42) CSF levels in AD patients (p = 0.003). A beta(40) levels were also lower in carriers of this haplotype; however, this did not reach statistical significance (p = 0.15). We found a SORL1 haplotype which was associated with CSF levels of amyloid-P cleavage products, measured as altered levels of A beta(42). Thus our data suggest that: SORL1 gene variants might influence AD pathology. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

引用

页码：68 / 71

页数：4

共 25 条

[1] Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein [J].