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
Andersen, OM
Reiche, J
Schmidt, V
Gotthardt, M
Spoelgen, R
Behlke, J
von Arnim, CAF
Breiderhoff, T
Jansen, P
Wu, X
Bales, KR
Cappai, R
Masters, CL
Gliemann, J
Mufson, EJ
Hyman, BT
Paul, SM
Nykjær, A
Willnow, TE
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (38) : 13461 - 13466
[2] Cerebrospinal fluid β-amyloid(1-42) in Alzheimer disease -: Differences between early- and late-onset Alzheimer disease and stability during the course of disease
Andreasen, N
Hesse, C
Davidsson, P
Minthon, L
Wallin, A
Winblad, B
Vanderstichele, H
Vanmechelen, E
Blennow, K
[J]. ARCHIVES OF NEUROLOGY, 1999, 56 (06) : 673 - 680
[3] A powerful strategy to account for multiple testing in the context of haplotype analysis
Becker, T
Knapp, M
[J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 75 (04) : 561 - 570
[4] CSF-tau, CSF-Aβ1-42, ApoE-genotype and clinical parameters in the diagnosis of Alzheimer's disease:: combination of CSF-tau and MMSE yields highest sensitivity and specificity
Ganzer, S
Arlt, S
Schoder, V
Buhmann, C
Mandelkow, EM
Finckh, U
Beisiegel, U
Naber, D
Müller-Thomsen, T
[J]. JOURNAL OF NEURAL TRANSMISSION, 2003, 110 (10) : 1149 - 1160
[5] HARTING V, 2000, DTSCH ADAPTATION REV
[6] HIXSON JE, 1990, J LIPID RES, V31, P545
[7] LEE JH, 2007, NEUROLOGY
[8] The association between genetic variants in SORL1 and Alzheimer disease in an urban, multiethnic, community-based cohort
Lee, Joseph H.
Cheng, Rong
Schupf, Nicole
Manly, Jennifer
Lantigua, Rafael
Stern, Yaakov
Rogaeva, Ekaterina
Wakutani, Yosuke
Farrer, Lindsay
St. George-Hyslop, Peter
Mayeux, Richard
[J]. ARCHIVES OF NEUROLOGY, 2007, 64 (04) : 501 - 506
[9] Neurochemical diagnosis of Alzheimer's dementia by CSF Aβ42, Aβ42/Aβ40 ratio and total tau
Lewczuk, P
Esselmann, H
Otto, M
Maler, JM
Henkel, AW
Henkel, MK
Eikenberg, O
Antz, C
Krause, WR
Reulbach, U
Kornhuber, J
Wiltfang, J
[J]. NEUROBIOLOGY OF AGING, 2004, 25 (03) : 273 - 281
[10] The German Competence Net Dementias: Standard operating procedures for the neurochemical dementia diagnostics
Lewczuk, P.
Kornhuber, J.
Wiltfang, J.
[J]. JOURNAL OF NEURAL TRANSMISSION, 2006, 113 (08) : 1075 - 1080

← 1 2 3 →