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Translational research in genomics of Alzheimer's disease: A review of current practice and future perspectives

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Author: Mihaescu, R. · Detmar, S.B. · Cornel, M.C. · Flier, W.M. van der · Heutink, P. · Hol, E.M. · Rikkert, M.G.M.O. · Duijn, C.M. van · Janssens, A.C.J.W.
Institution: TNO Kwaliteit van leven
Source:Journal of Alzheimer's Disease, 4, 20, 967-980
Identifier: 408461
Keywords: Health · Leefomgeving en gezondheid · Alzheimer's disease · genomics · review · translational research · amyloid precursor protein · antidepressant agent · antiinflammatory agent · apolipoprotein C1 · apolipoprotein C2 · apolipoprotein E · bapineuzumab · cholinergic receptor stimulating agent · clathrin assembly protein · clozapine · complement component C3b receptor · cystatin C · disrupted in schizophrenia 1 protein · endothelial nitric oxide synthase · galantamine · growth factor receptor bound protein 2 · growth hormone · mitochondrial transcription factor A · phosphatidylinositol · phosphoenolpyruvate carboxykinase (GTP) · presenilin 1 · presenilin 2 · progranulin · risperidone · rosiglitazone · sortilin · tau protein · transient receptor potential channel 4 · unindexed drug · zinc finger protein · Alzheimer disease · autosomal dominant inheritance · clinical trial · diagnostic accuracy · differential diagnosis · drug efficacy · early diagnosis · evidence based medicine · evidence based practice · gene expression profiling · gene locus · genetic analysis · genetic association · genetic counseling · genetic polymorphism · genetic risk · genetic screening · genetic variability · genomics · genotype · health care management · high risk patient · high risk population · human · incidence · medical research · pharmacogenomics · practice guideline · prediction · priority journal · review · treatment response


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. © 2010 - IOS Press and the authors. All rights reserved.