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Fine mapping of 10q and 18q for familial Alzheimer's disease in Caribbean Hispanics

Molecular Psychiatry volume 9, pages 1042–1051 (2004)Cite this article

Abstract

Familial Alzheimer's disease (AD [MIM 104300]) has been a focus of intense investigation, primarily in Caucasian families from Europe and North America families. Although the late-onset form of familial AD, beginning after age 65 years, has been linked to regions on chromosomes 10q and 12p, the specific genetic variants have not yet been consistently identified. Using a unique cohort of families of Caribbean Hispanics ancestry, we screened the genome using 340 markers on 490 family members from 96 families with predominantly late-onset AD. We observed the strongest support for linkage on 18q (LOD=3.14). However, 17 additional markers (chromosomes 1–6, 8, 10, 12, and 14) exceeded a two-point LOD score of 1.0 under the affecteds-only autosomal dominant model or affected sibpair model. As we previously reported the fine-mapping effort on 12p showing modest evidence of linkage, we focused our fine-mapping efforts on two other candidate regions in the current report, namely 10q and 18q. We added 31 family members and eight additional Caribbean Hispanic families to fine map 10q and 18q. With additional microsatellite markers, the evidence for linkage for 18q strengthened near 112 cM, where the two-point LOD score for D18S541 was 3.37 and the highest NPL score in that region was 3.65 (P=0.000177). This narrow region contains a small number of genes expressed in the brain. However, at 10q (134–138 cM), the NPL score decreased from 3.15 (P=0.000486) to 2.1 (P=0.0218), but two broad peaks remained overlapping with previously reported peaks. Our results provide modest support for linkage on 10q and 12p in this cohort of Caribbean Hispanic families with familial Alzheimer's disease, and strong evidence for a new locus on 18q.

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Acknowledgements

Support to this work was provided by Federal Grants AG15473, AG08702, AG07232, Alzheimer's Association grant IIRG-02-4387, the Charles S Robertson Memorial Gift for Alzheimer's Disease Research from the Banbury Fund and the Blanchette Hooker Rockefeller Foundation. We also thank the members of Estudio Familiar de Influencia Genetica en Alzheimer, The Sociedad Dominicana de Geriatria y Gerontologia, The Sociedad Dominicana de Neurologia y Neurocirugia, The Sociedad Dominicana de Psiquiatria and the Associacion Dominicana Alzheimer y Similares, Inc, and The Bioethics National Committee for Research in the Dominican Republic.

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  1. J H Lee and R Mayeux: These authors contributed equally to the work involved in this investigation.

Authors and Affiliations

  1. The Taub Institute on Alzheimer's Disease and the Aging Brain, Columbia University, New York, USA

    J H Lee, R Mayeux, J Williamson, A Flaquer, R Lantigua, Y Stern, B Tycko & J A Knowles

  2. The Gertrude H. Sergievsky Center, Columbia University, New York, USA

    J H Lee, R Mayeux, V Santana, J Williamson, A Flaquer, H Rondon, P Estevez & Y Stern

  3. Department of Neurology, College of Physicians Surgeons, Columbia University, New York, USA

    R Mayeux & Y Stern

  4. Department of Psychiatry, College of Physicians Surgeons, Columbia University, New York, USA

    R Mayeux, D Mayo, J Mo, Y Stern & J A Knowles

  5. Department of Medicine, College of Physicians Surgeons, Columbia University, New York, USA

    R Lantigua

  6. Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, USA

    A Ciappa & B Tycko

  7. Department of Epidemiology, School of Public Health, Columbia University, New York, USA

    J H Lee & R Mayeux

  8. The Columbia Genome Center, Columbia University, New York, USA

    D Mayo, J Mo & J A Knowles

  9. The New York State Psychiatric Institute, New York, USA

    D Mayo, J Mo & J A Knowles

  10. The Universidad Tecnologica de Santiago, Dominican Republic

    M Medrano

  11. The Plaza de la Salud Hospital, Dominican Republic

    H Rondon & M Torres

  12. University of Toronto and Department of Medicine, Centre for Research in Neurodegenerative Diseases, University Health Network, Toronto, Ontario, Canada

    T Kawarai, A Toulina, E Rogaeva & P St. George-Hyslop

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  1. J H Lee
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Correspondence to R Mayeux.

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Supplementary information accompanies the paper on Molecular Psychiatry website (http://www.nature.com/mp)

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Lee, J., Mayeux, R., Mayo, D. et al. Fine mapping of 10q and 18q for familial Alzheimer's disease in Caribbean Hispanics. Mol Psychiatry 9, 1042–1051 (2004). https://doi.org/10.1038/sj.mp.4001538

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