Properties of TCR gamma clonotypes in AD brain and peripheral blood: Development of new models and analysis methods/neuroinflammation. (7th December 2020)

• Record Type: Journal Article
• Authors: Aliseychik, Maria P.; Patrikeev, Anton; Gusev, Fedor; Grigorenko, Anastasia; Andreeva, Tatiana; Biragyn, Arya; Rogaev, Evgeny I.
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 2
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.042028
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: The immune system contributes to various neurodegenerative pathologies, including Alzheimer's disease (AD). γδ T cells can mediate different pathological processes in the human brain, such as oncogenesis, autoimmunity, and stroke. However, the role of γδ T cells in AD have not yet been elucidated. Method: We designed an approach based on multiplex PCR system with following library preparation and deep sequencing of the CDR3 region of TRGs. In total clonotype repertoires from 147 peripheral blood and postmortem brain samples of AD patients and control individuals without dementia were analyzed. Moreover 17 blood repertoires of patients with Parkinson's disease (PD) were also tested. Result: Our results showed special features of peripheral blood (PB) and brain TRG repertoires: compared with the PB, the brain showed reduced TRGV9 clonotypes but was enriched in TRGV2/4/8 clonotypes. Age‐related changes were found. The reduced diversity and CDR3 length of human blood TRG repertoires and in the composition of the brain TRG repertoire, in particular, a decrease in the frequency of the TRGV9 segments and an increase in TRGV2/4/8 were identified. We developed a bioinformatic approach based on the physicochemical properties analysis of rare clones that are found in patients with AD but not in healthy individuals. Our findings revealed the enrichment of TRG clonotypes with specific properties in the brain or blood of patients with AD compared to those in controls. (Aliseychik et al. 2020) These AD‐associated clonotypes are not typical for patients with PD, for which accumulation of the AD specific clonotypes was not pronounced. Conclusion: The pilot study of TCR repertoires in AD revealed disease associated TRGs profile properties in brain and blood and implied putative AD‐associated immunogenic markers. This work was supported by the National Institute on Aging (NIA; R01 AG054712); the Russian Foundation for Basic Research (RFBR, grant no. 18‐29‐13051) and the Russian Science Foundation (RSF, grant no. 19‐75‐30039).