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Despite the fact that only modest adaptive immune system related approaches to treating Alzheimer’s disease (AD) are available, an immunogenomics approach to the study of Alzheimer’s disease has not yet substantially advanced.  Thus, we characterized T-cell receptor alpha (TRA) complementarity determining region-3 (CDR3) physicochemical features and identified TRA CDR3 homology groups, represented by TRA recombination reads extracted from 2665 AD-related, blood- and brain-derived exome files.   We found that a higher isoelectric value for the brain TRA CDR3s was associated with a higher (clinically worse) Braak stage and that a number of TRA CDR3 chemical homology groups, in particular representing bloodborne TRA CDR3s, were associated with higher or lower Braak stages.  Lastly, greater chemical complementarity of both blood- and brain-derived TRA CDR3s and Tau, based on a recently described CDR3-candidate antigen chemical complementarity scoring process (, was associated with higher Braak stages.  Overall, the data reported here raise the questions of (a) whether progression of AD is facilitated by the adaptive immune response to Tau; and (b) whether assessment of such an anti-Tau immune response could potentially serve as a basis for adaptive immune receptor related, AD risk stratification?

Data represent the extraction of TRA recombination reads from the Alzheimer’s Disease Sequencing Project (ADSP) brain and blood exome files, as described in detail in PMID 35662120 PubMed link.

Available Filesets

NameAccessionLatest ReleaseDescription
AD IR Recombos: Supporting online material for PMID 35662120fsa000058NG00148.v1Supporting online material for PMID 35662120

View the File Manifest for a full list of files released in this dataset.

Acknowledgment statement for any data distributed by NIAGADS:

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

Use the study-specific acknowledgement statements below (as applicable):

For investigators using any data from this dataset:

Please cite/reference the use of NIAGADS data by including the accession NG00148.

For investigators using Alzheimer's disease (AD) and immune receptor recombinations (sa000035) data:

Please acknowledge PMID 35662120

Huda TI, et al. Immunogenomics Parameters for Patient Stratification in Alzheimer’s Disease. J Alzheimers Dis. 2022;88(2):619-629. doi: 10.3233/JAD-220119. PMID: 35662120. PubMed link