Full access

New Research

Published Online: 1 October 2011

Association of the Alzheimer's Gene SORL1 With Hippocampal Volume in Young, Healthy Adults

Janita Bralten, M.S., Alejandro Arias-Vásquez, Ph.D., Remco Makkinje, B.S., Joris A. Veltman, Ph.D., Han G. Brunner, M.D., Ph.D., Guillén Fernández, M.D., Ph.D., Mark Rijpkema, Ph.D., and Barbara Franke, Ph.D.Authors Info & Affiliations

Publication: American Journal of Psychiatry

Volume 168, Number 10

https://doi.org/10.1176/appi.ajp.2011.10101509

PDF/EPUB OtherFormats

Abstract

Variants in SORL1 have previously been established to increase the risk for Alzheimer's disease. The findings from this study that multiple variants in SORL1 contributed to decreased hippocampal size suggest a biological basis for this effect and thus raise the possibility that it might be prevented.

Abstract

Objective:

Alzheimer's disease is among the most common neurodegenerative disorders. The SORL1 (sortilin receptor 1) gene is associated with the disease, but different variants seem to contribute. The authors used a gene-wide approach to test whether SORL1 is associated with volume of the hippocampus, one of the first structures to be affected by Alzheimer's disease in young, healthy individuals, in an attempt to map potential pathways from gene to disease.

Method:

Individuals were genotyped using an array-based method, and a total of 117 single nucleotide polymorphisms (SNPs) in and surrounding SORL1 were included in the analysis. Through the use of a brain segmentation protocol, SNP-by-SNP and gene-wide associations with bilateral hippocampal volume were assessed in two large, independent samples consisting of 446 (discovery cohort) and 490 (replication cohort) healthy young individuals.

Results:

Significant association of the SORL1 gene with hippocampal volume was observed in both the discovery and replication samples as well as in the combined sample. The gene-wide association was independent of the apolipoprotein E genotype and resistant to removal of four significantly associated single SNPs.

Conclusions:

This study provides the first evidence that the SORL1 gene is associated with differences in hippocampal volume in young, healthy adults. It is demonstrated that gene-wide analysis techniques may overcome power problems caused by allelic heterogeneity in association studies. The results support the hypothesis that the SORL1 gene contributes to an increased risk for Alzheimer's disease through effects on hippocampal volume.

Formats available

You can view the full content in the following formats:

View PDF/EPUB View Full Text

Information & Authors

Information

Published In

American Journal of Psychiatry

Volume 168 • Number 10 • October 2011

Pages: 1083 - 1089

PubMed: 21730226

History

Received: 19 October 2010

Revision received: 3 January 2011

Revision received: 17 February 2011

Accepted: 14 March 2011

Published online: 1 October 2011

Published in print: October 2011

Authors

Details

Janita Bralten, M.S.

From the Department of Human Genetics and Department of Cognitive Neurosciences, Radboud University Nijmegen Medical Centre;and the Department of Psychiatry and the Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.

View all articles by this author

Alejandro Arias-Vásquez, Ph.D.

View all articles by this author

Remco Makkinje, B.S.

View all articles by this author

Joris A. Veltman, Ph.D.

View all articles by this author

Han G. Brunner, M.D., Ph.D.

View all articles by this author

Guillén Fernández, M.D., Ph.D.

View all articles by this author

Mark Rijpkema, Ph.D.

View all articles by this author

Barbara Franke, Ph.D.

View all articles by this author

Notes

Address correspondence to Dr. Franke ([email protected]).

Author Contributions

Ms. Bralten and Dr. Arias-Vásquez contributed equally to this study.

Funding Information

The authors report no financial relationships with commercial interests.Funded in part by the Hersenstichting Nederland, Den Haag, the Netherlands.

Metrics & Citations

Metrics

Citations

Export Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format	RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks
Direct importt
Citation style
Style

Copy to clipboard
Tips for downloading citations

View Options

View options

PDF/EPUB

View PDF/EPUB

Full Text

View Full Text

Get Access

Login options

Already a subscriber? Access your subscription through your login credentials or your institution for full access to this article.

Personal login Institutional Login Open Athens login

Purchase Options

Purchase this article to access the full text.

PPV Articles - American Journal of Psychiatry

Not a subscriber?

Subscribe Now / Learn More

PsychiatryOnline subscription options offer access to the DSM-5-TR^® library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

Association of the Alzheimer's Gene SORL1 With Hippocampal Volume in Young, Healthy Adults

Abstract