Alzheimer's disease (AD) and immune receptor recombinations

We would like to access the exome files for Alzheimer’s Disease (AD) studies to better ascertain the impact of certain immune receptor (IR) recombinations on the progression of Alzheimer’s patients. First, we will mine the exomes for all IR recombinations present in the AD exome files using our previously published algorithms and software [4-6, 9]. These studies have been successful in identifying IR recombination reads that were strongly associated with distinct survival rates in various cancers. In particular, we have been able to utilize a similar methodology to identify specific T-Cell recombinations associated with cancer features by using the recombinations that are obtained from blood sample exomes. For example, recently published papers from our group have revealed consistent features of T-cell receptor recombinations, obtained from cancer patient blood samples, which were associated with features of cancer progression [4, 8]. Therefore, we hypothesize that we can detect specific IR recombination features from blood-resident T- or B-cells that are relevant to AD clinical features.
Thus, we will first identify IR recombinations found within the AD, blood exomes; and then match features of these IRs, such as the chemical aspects of the IR antigen binding sites [1, 4, 5] with clinical characteristics, e.g., age of onset, diagnostic status, and cognitive measures. We thus expect to identify certain IR recombinations associated with distinct prognoses.
It should also be noted that there have been previous studies linking HLA-DR alleles to late-onset AD [10]. This is of particular interest, because of our previous work linking T-cell receptor, V or J usage, HLA allele combinations to distinct cancer survival rates [2, 3, 7, 8]. Thus, we will also programmatically obtain the HLA alleles from the exome files and determine whether any T-cell receptor, V or J usage, HLA allele combinations are associated with particular features of AD development.

References available by email: gblanck@usf.edu

The purpose of this project is to learn whether there are any features of the immune system that are unique to Alzheimer's patients. If so, such unique features might help understand disease progression better and might provide targets for therapies.