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Apolipoprotein E is associated with age at onset of amyotrophic lateral sclerosis

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Abstract

Apolipoprotein E (APOE) is a confirmed risk factor for Alzheimer disease. APOE is also involved in several other neurodegenerative disorders, including Parkinson disease and multiple sclerosis. Previous studies of amyotrophic lateral sclerosis (Lou Gehrig disease, ALS) have investigated the effect of APOE on the risk of developing ALS, age at onset, site of onset, and duration of the disease. The results have been inconsistent, possibly due to small sample sizes and complete reliance on case-control data. No family-based association studies were performed. To address these limitations, we investigated the relationship between APOE functional polymorphisms and age at onset of ALS in a large set of 508 families. We treated age at onset as a quantitative trait and performed family-based association analysis using the TDT Q5 method. APOE-2 is protective against earlier onset ( P =0.001) with an average age at onset of APOE-2 carriers approximately 3 years later than that of non-APOE-2 carriers. Similar to our previous report, we did not find APOE associated with ALS risk. Our findings suggest that APOE may express its strongest effect through age at onset rather than on risk.

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Acknowledgements

We would like to thank the families and patients with ALS for their participation in this study. Without their help this work would not have been possible. This research was supported by the National Institute of Neurological Disorders and Stroke (NS 37912, NS021442), Les Turner ALS Foundation, Vena E. Schaff ALS Research Fund, Harold Post Research Professorship, Herbert and Florence C. Wenske Foundation, Ralph and Marian Falk Medical Research Trust, Abbott Labs Duane, and Susan Burnham Professorship. R.H.’s laboratory also receives support for this work from the NINDS, the NIA, project ALS, the Angel Fund, the ALS Association, and the Al-Athel ALS Research Foundation. P.S. is supported through the laboratory of H.R. Horvitz, an investigator of the Howard Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Mass.

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Correspondence to Yi-Ju Li.

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R.H. Brown Jr and T. Siddique contributed equally to this project.

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Li, YJ., Pericak-Vance, M.A., Haines, J.L. et al. Apolipoprotein E is associated with age at onset of amyotrophic lateral sclerosis. Neurogenetics 5, 209–213 (2004). https://doi.org/10.1007/s10048-004-0193-0

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