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Genetic loci associated with Alzheimer's disease and cerebrospinal fluid biomarkers in a Finnish case-control cohort.
PLoS One 2013; 8(4):e59676Plos

Abstract

OBJECTIVES

To understand the relation between risk genes for Alzheimer's disease (AD) and their influence on biomarkers for AD, we examined the association of AD in the Finnish cohort with single nucleotide polymorphisms (SNPs) from top AlzGene loci, genome-wide association studies (GWAS), and candidate gene studies; and tested the correlation between these SNPs and AD markers Aβ(1-42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF).

METHODS

We tested 25 SNPs for genetic association with clinical AD in our cohort comprised of 890 AD patients and 701-age matched healthy controls using logistic regression. For the correlational study with biomarkers, we tested 36 SNPs in a subset of 222 AD patients with available CSF using mixed models. Statistical analyses were adjusted for age, gender and APOE status. False discovery rate for multiple testing was applied. All participants were from academic hospital and research institutions in Finland.

RESULTS

APOE-ε4, CLU rs11136000, and MS4A4A rs2304933 correlated with significantly decreased Aβ(1-42) (corrected p<0.05). At an uncorrected p<0.05, PPP3R1 rs1868402 and MAPT rs2435211 were related with increased t-tau; while SORL1 rs73595277 and MAPT rs16940758, with increased p-tau. Only TOMM40 rs2075650 showed association with clinical AD after adjusting for APOE-ε4 (p = 0.007), but not after multiple test correction (p>0.05).

CONCLUSIONS

We provide evidence that APOE-ε4, CLU and MS4A4A, which have been identified in GWAS to be associated with AD, also significantly reduced CSF Aβ1-42 in AD. None of the other AlzGene and GWAS loci showed significant effects on CSF tau. The effects of other SNPs on CSF biomarkers and clinical AD diagnosis did not reach statistical significance. Our findings suggest that APOE-ε4, CLU and MS4A4A influence both AD risk and CSF Aβ1-42.

Authors+Show Affiliations

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23573206

Citation

Elias-Sonnenschein, Lyzel S., et al. "Genetic Loci Associated With Alzheimer's Disease and Cerebrospinal Fluid Biomarkers in a Finnish Case-control Cohort." PloS One, vol. 8, no. 4, 2013, pp. e59676.
Elias-Sonnenschein LS, Helisalmi S, Natunen T, et al. Genetic loci associated with Alzheimer's disease and cerebrospinal fluid biomarkers in a Finnish case-control cohort. PLoS ONE. 2013;8(4):e59676.
Elias-Sonnenschein, L. S., Helisalmi, S., Natunen, T., Hall, A., Paajanen, T., Herukka, S. K., ... Hiltunen, M. (2013). Genetic loci associated with Alzheimer's disease and cerebrospinal fluid biomarkers in a Finnish case-control cohort. PloS One, 8(4), pp. e59676. doi:10.1371/journal.pone.0059676.
Elias-Sonnenschein LS, et al. Genetic Loci Associated With Alzheimer's Disease and Cerebrospinal Fluid Biomarkers in a Finnish Case-control Cohort. PLoS ONE. 2013;8(4):e59676. PubMed PMID: 23573206.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic loci associated with Alzheimer's disease and cerebrospinal fluid biomarkers in a Finnish case-control cohort. AU - Elias-Sonnenschein,Lyzel S, AU - Helisalmi,Seppo, AU - Natunen,Teemu, AU - Hall,Anette, AU - Paajanen,Teemu, AU - Herukka,Sanna-Kaisa, AU - Laitinen,Marjo, AU - Remes,Anne M, AU - Koivisto,Anne M, AU - Mattila,Kari M, AU - Lehtimäki,Terho, AU - Verhey,Frans R J, AU - Visser,Pieter Jelle, AU - Soininen,Hilkka, AU - Hiltunen,Mikko, Y1 - 2013/04/03/ PY - 2012/11/29/received PY - 2013/02/16/accepted PY - 2013/4/11/entrez PY - 2013/4/11/pubmed PY - 2013/10/23/medline SP - e59676 EP - e59676 JF - PloS one JO - PLoS ONE VL - 8 IS - 4 N2 - OBJECTIVES: To understand the relation between risk genes for Alzheimer's disease (AD) and their influence on biomarkers for AD, we examined the association of AD in the Finnish cohort with single nucleotide polymorphisms (SNPs) from top AlzGene loci, genome-wide association studies (GWAS), and candidate gene studies; and tested the correlation between these SNPs and AD markers Aβ(1-42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). METHODS: We tested 25 SNPs for genetic association with clinical AD in our cohort comprised of 890 AD patients and 701-age matched healthy controls using logistic regression. For the correlational study with biomarkers, we tested 36 SNPs in a subset of 222 AD patients with available CSF using mixed models. Statistical analyses were adjusted for age, gender and APOE status. False discovery rate for multiple testing was applied. All participants were from academic hospital and research institutions in Finland. RESULTS: APOE-ε4, CLU rs11136000, and MS4A4A rs2304933 correlated with significantly decreased Aβ(1-42) (corrected p<0.05). At an uncorrected p<0.05, PPP3R1 rs1868402 and MAPT rs2435211 were related with increased t-tau; while SORL1 rs73595277 and MAPT rs16940758, with increased p-tau. Only TOMM40 rs2075650 showed association with clinical AD after adjusting for APOE-ε4 (p = 0.007), but not after multiple test correction (p>0.05). CONCLUSIONS: We provide evidence that APOE-ε4, CLU and MS4A4A, which have been identified in GWAS to be associated with AD, also significantly reduced CSF Aβ1-42 in AD. None of the other AlzGene and GWAS loci showed significant effects on CSF tau. The effects of other SNPs on CSF biomarkers and clinical AD diagnosis did not reach statistical significance. Our findings suggest that APOE-ε4, CLU and MS4A4A influence both AD risk and CSF Aβ1-42. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23573206/Genetic_loci_associated_with_Alzheimer's_disease_and_cerebrospinal_fluid_biomarkers_in_a_Finnish_case_control_cohort_ L2 - http://dx.plos.org/10.1371/journal.pone.0059676 DB - PRIME DP - Unbound Medicine ER -