Brain Advance Access published online on May 6, 2004
Brain, doi:10.1093/brain/awh179
© 2004 by Guarantors of Brain
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Genetic Epidemiology Unit, Departments of Epidemiology and Biostatistics and Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: c.vanduijn{at}erasmusmc.nl.
Despite advances in elucidating the genetic epidemiology of Alzheimer’s disease and frontotemporal dementia, the aetiology for most patients with dementia remains unclear. We examined the genetic epidemiology of dementia in a recent genetically isolated Dutch population founded around 1750. The series of 191 patients ascertained comprised 122 probable Alzheimer’s disease patients with late onset and 17 with early onset, and 22 with possible Alzheimer’s disease. It further included 10 patients with vascular dementia, nine with Lewy body dementia and six with frontotemporal dementia. All patients, except those with vascular dementia, were more closely related than healthy individuals from the same area. Clustering was strongest for patients with early-onset Alzheimer’s disease or Lewy body dementia. Although 14% of late-onset Alzheimer’s disease patients had evidence of autosomal dominant disease, consanguinity was found in three late-onset Alzheimer’s disease patients, suggesting a recessive or polygenic model underlying the trait. We found no clustering of vascular dementia, implying a difference in genetic risk for late-onset Alzheimer’s disease and vascular dementia. Mutations in known genes could not explain the occurrence of dementia, but the population attributable proportion of apolipoprotein E gene (APOE4) was high (45%) due to a high frequency of APOE4 carriers. Earlier identified regions on chromosomes 10 and 12, nor the effect of the alpha-2-macroglobulin (A2M) I/D polymorphism on Alzheimer’s disease could be confirmed in our study. We did find evidence for association between the A2M D-allele and Lewy body dementia. Our data showed a strong familial clustering of various forms of dementia in this isolated Dutch population. A high percentage of late-onset Alzheimer’s disease could be explained by APOE4, but 55% of its origin is still unknown. Key Words:
dementia; familial aggregation; genetically isolated population
Revised February 5, 2004
Accepted March 8, 2004
Article
Familial clustering and genetic risk for dementia in a genetically isolated Dutch population
2 Genetic Epidemiology Unit, Departments of Epidemiology and Biostatistics and Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands; Department of Neurology, St Elisabeth Hospital, Tilburg, The Netherlands
3 Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Belgium
4 Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
5 Genetic Epidemiology Unit, Departments of Epidemiology and Biostatistics and Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands; Department of Human Genetics, VU University Medical Centre, Amsterdam, The Netherlands
6 Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. L. Berends, C. J.M. de Groot, E. J. Sijbrands, M. P.S. Sie, S. H. Benneheij, R. Pal, R. Heydanus, B. A. Oostra, C. M. van Duijn, and E. A.P. Steegers Shared Constitutional Risks for Maternal Vascular-Related Pregnancy Complications and Future Cardiovascular Disease Hypertension, April 1, 2008; 51(4): 1034 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Patterson MD, J. W. Feightner MD MSc, A. Garcia MD PhD, G.-Y. R. Hsiung MD MHSc, C. MacKnight MD MSc, and A. D. Sadovnick PhD Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease Can. Med. Assoc. J., February 26, 2008; 178(5): 548 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. L. Ber, E. Guedj, A. Gabelle, P. Verpillat, M. Volteau, C. Thomas-Anterion, M. Decousus, D. Hannequin, P. Vera, L. Lacomblez, et al. Demographic, neurological and behavioural characteristics and brain perfusion SPECT in frontal variant of frontotemporal dementia. Brain, November 1, 2006; 129(Pt 11): 3051 - 3065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Brouwers, K. Sleegers, S. Engelborghs, V. Bogaerts, S. Serneels, K. Kamali, E. Corsmit, E. D. Leenheir, J.-J. Martin, P. P. De Deyn, et al. Genetic risk and transcriptional variability of amyloid precursor protein in Alzheimer's disease Brain, November 1, 2006; 129(11): 2984 - 2991. [Abstract] [Full Text] [PDF]
|
|