Translational Research in Genomics of Alzheimer's Disease: A Review of Current Practice and Future Perspectives

Article type: Review Article

Authors: Mihaescu, Raluca^a | Detmar, Symone B.^b | Cornel, Martina C.^c | van der Flier, Wiesje M.^d | Heutink, Peter^e | Hol, Elly M.^f | Rikkert, Marcel G.M. Olde^g | van Duijn, Cornelia M.^a | Janssens, A. Cecile J.W.^{a; *}

Affiliations: [a] Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands | [b] TNO Quality of Life, Leiden, The Netherlands | [c] Community Genetics, Department of Clinical Genetics/EMGO Institute, VU University Medical Center, Amsterdam, The Netherlands | [d] Alzheimer Center and Department of Neurology, Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands | [e] Department of Clinical Genetics, Section of Medical Genomics, VU University Medical Center, Amsterdam, The Netherlands | [f] Department of Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands | [g] Department of Geriatrics, Alzheimer Center Nijmegen, Radboud University Hospital Nijmegen, Nijmegen, The Netherlands

Correspondence: [*] Correspondence to: A. Cecile J.W. Janssens, Department of Epidemiology, Erasmus University Medical Center, Postbox 2040, 3000 CA Rotterdam, The Netherlands. Tel.: +31 10 704 4232; Fax: +31 10 704 4657; E-mail: a.janssens@erasmusmc.nl.

Note: [1] Handling Associate Editor: Inga Zerr

Abstract: Alzheimer's disease (AD) is the most prevalent form of dementia and the number of cases is expected to increase exponentially worldwide. Three highly penetrant genes (AβPP, PSEN1, and PSEN2) explain only a small number of AD cases with a Mendelian transmission pattern. Many genes have been analyzed for association with non-Mendelian AD, but the only consistently replicated finding is APOE. At present, possibilities for prevention, early detection, and treatment of the disease are limited. Predictive and diagnostic genetic testing is available only in Mendelian forms of AD. Currently, APOE genotyping is not considered clinically useful for screening, presymptomatic testing, or clinical diagnosis of non-Mendelian AD. However, clinical management of the disease is expected to benefit from the rapid pace of discoveries in the genomics of AD. Following a recently developed framework for the continuum of translation research that is needed to move genetic discoveries to health applications, this paper reviews recent genetic discoveries as well as translational research on genomic applications in the prevention, early detection, and treatment of AD. The four phases of translation research include: 1) translation of basic genomics research into a potential health care application; 2) evaluation of the application for the development of evidence-based guidelines; 3) evaluation of the implementation and use of the application in health care practice; and 4) evaluation of the achieved population health impact. Most research on genome-based applications in AD is still in the first phase of the translational research framework, which means that further research is still needed before their implementation can be considered.

Keywords: Alzheimer's disease, genomics, review, translational research

DOI: 10.3233/JAD-2010-1410

Journal: Journal of Alzheimer's Disease, vol. 20, no. 4, pp. 967-980, 2010