UCLA

Frontotemporal Dementia (FTD) is a progressive, terminal neurodegenerative disorder with a strong genetic component in individual risk. Prior FTD genetic-wide association studies (GWAS) have identified several disease-associated single nucleotide polymorphisms (SNPs) including lead SNPs adjacent to HLA loci, one of which has also been implicated in immunosenescence. As HLA is a major component of immune activation, understanding the role of HLA genetic variation in FTD pathology and senescence may lead to uncovering causal roles of immune pathways in neurodegeneration. We hypothesize that genetic variation in HLA gene or gene-regulatory regions is driving HLA expression and immune response in disease. To support this hypothesis, we seek to define HLA haplotypes and alleles associated with clinical outcomes and disease pathologies. We use a new but proven methodology that can overcome the challenges of studying the most polymorphic gene region in the human genome that has yet to be applied to FTD cohorts.