1. ¹Department of Neurobiology, Care Sciences and Society, Karolinska Institutet Dainippon Sumitomo Pharma Alzheimer Center (KASPAC), Karolinska Institutet, Huddinge, Sweden
2. ²Department of Biotechnology, AlbaNova University Center, Royal Institute of Technology (KTH), Stockholm, Sweden

Correspondence: Dr C Graff, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet Dainippon Sumitomo Pharma Alzheimer Center (KASPAC), Karolinska Institutet, Novum level 5, Huddinge SE-14157, Sweden. Tel: +46 8 585 836 19; Fax: +46 8 585 836 10; E-mail: Caroline.Graff@ki.se

Received 14 May 2007; Revised 26 September 2007; Accepted 27 September 2007; Published online 24 October 2007.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease that affects approximately 20 million persons all over the world. There are both sporadic and familial forms of AD. We have previously reported a genome-wide linkage analysis on 71 Swedish AD families using 365 genotyped microsatellite markers. In this study, we increased the number of individuals included in the original 71 analysed families besides adding 38 new families. These 109 families were genotyped for 1100 novel microsatellite markers. The present study reports on the linkage data generated from the non-overlapping genotypes from the first genome scan and the genotypes of the present scan, which results in a total of 1289 successfully genotyped markers at an average density of 2.85 cM on 468 individuals from 109 AD families. Non-parametric linkage analysis yielded a significant multipoint LOD score in chromosome 19q13, the region harbouring the major susceptibility gene APOE, both for the whole set of families (LOD=5.0) and the APOE 4-positive subgroup made up of 63 families (LOD=5.3). Other suggestive linkage peaks that were observed in the original genome scan of 71 Swedish AD families were not detected in this extended analysis, and the previously reported linkage signals in chromosomes 9, 10 and 12 were not replicated.