P1-303: Low levels of sRAGE plasma concentration in different types of dementia (original) (raw)

Background: Late-onset Alzheimer's disease is a complex neurodegenerative disorder characterized by cognitive decline and distinct neuropathology. Multiple genes will be linked/associated with the disease. While case/control association studies are informative in the identification of risk factors, large extended pedigrees may be more useful in identifying genetic variants linked with the disease. Objective: To identify the mutations in the candidate genes linked with the disease in our large extended pedigrees. Methods: Our family 28 has 14 siblings, 5 affected with late-onset Alzheimer's disease and two of the father's siblings also affected with the disease. We have DNA on all of the siblings, including the five affected siblings, on the two affected of the father's siblings, on one of the mother's unaffected siblings, on many children and spouses, for a total of 63 samples. The clinical diagnosis was made according to the NINCDS-ADRDA criteria. In addition, we included an MRI of the brain, showing cortical atrophy with no evidence of strokes or tumors. Using a microsatellite scan of the DNA, we identified a location on chromosome 12 with a significant LOD score that was linked with the disease in family 28. Since the location was large containing many genes, we used the 100 K SNP microarrays for further analysis. We have identified several locations on chromosome 12 as well as locations on two other chromosomes that are associated with the disease. We are in the process of analyzing additional tag SNPs and microsatellites in candidate genes, before we begin resequencing to identify the genetic variations linked with the disease in this family. Conclusions: The use of extended pedigrees with multiple affected members may be more useful in identifying genetic variants linked with complex diseases.