A LRPAP1 intronic insertion/deletion polymorphism and phenotypic variability in Alzheimer disease

Alzheimer disease (AD) is a neurodegenerative disorder, characterized by dementia. AD exhibits variability in age at onset, rate of progression, and specific cognitive, functional, and behavioral features. Genetic variants are potential modulators of phenotypic variability. The purpose of this study was to explore the relationship between a polymorphism in the Low Density Lipoprotein Receptor Related Protein-Associated Protein (LRPAP1) gene (4p16.3) and repeated measures of cognition, function, and behavior in persons with AD, using outcome data collected in two caregiver intervention studies. Thirty-seven subjects diagnosed with probable or possible AD were recruited. All subjects were genotyped for a 37 basepair insertion/deletion polymorphism in intron 5 of the LRPAP1 gene. No differences in allele or genotype frequencies by gender or by age at onset were identified. No statistically significant genotype effects upon cognition or behavior were identified. However, trends were noted in measures of language, with the LRPAP1 insertion-positive subjects exhibiting poorer language scores (average score difference = 28%, p = .158). LRPAP1 insertion-positive subjects also were more functionally impaired than subjects without the LRPAP1 insertion allele (F1,7 = 7.36, p = .030). These results suggest genetic variations at the LRPAP1 locus may modulate AD phenotype beyond risk for disease.