Alzheimer’s disease (AD) and immune receptor recombinations

A further understanding of the potential role of the adaptive immune receptor (IR)s in AD is needed.  In the first report of IR recombination reads obtained via mining AD+ blood or brain genomics files, we characterized T-cell receptor (TCR) recombination reads from blood and brain-derived, AD patient exome (WXS) files obtained from the Alzheimer’s Disease Sequencing Project (ADSP).  We utilized an approach that employs a novel chemical complementarity assessment for complementarity determining region-3 (CDR3)s and candidate antigens designed for the big data setting.  Results indicated a correlation of higher AD+ patient Braak stages with increased chemical complementarity scores for both the blood and brain-derived T-cell receptor alpha (TRA) CDR3s and tau.  Specifically, the most important part of TRA for antigen binding, the CDR3, varies with regard to the chemical features of its AAs, and subcategories of this variation can be linked to different Braak stage categories. This indicates a potential future opportunity to establish immunogenomics parameters for risk stratification in AD.  (Taken from PMID 35662120 PubMed link)