Fig. 1: ARIA is associated with expansion of peripheral CD8⁺ TEMRA cells.
From: Clonal expansion of cytotoxic CD8⁺ T cells in lecanemab-associated ARIA
a Representative MRIs show edema/effusions on T2-FLAIR/TIRM (blue triangles) and microhemorrhages/siderosis on SWI (orange triangles) from three selected ARIA cases (ARIA-E, ARIA-H, and ARIA-E/H). Cases were matched to three controls by age, sex, APOE genotype, and infusion number. “Baseline” indicates pre-treatment MRI; “At diagnosis” indicates surveillance MRI when ARIA was first detected. Clinical characteristics provided in Supplemental Table 1. b Study design and multi-omic profiling workflow (Created in BioRender. Morganti, J. (2026) https://BioRender.com/9hv27wi). PBMCs collected pre-infusion underwent 5′ scRNA-seq with CITE-seq and V(D)J, plus targeted metabolomics. c, d Multimodal (RNA + Antibody-Derived Tags (ADT)) UMAP of ~117,000 cells resolves major PBMC lineages (T, B, NK, monocytes, DCs). e Proportions of major lymphocyte classes show increased CD8⁺ and decreased CD4⁺ frequencies in ARIA+ subjects. f Routine clinical counts reveal similar CBC differentials across groups, with a trend toward higher absolute lymphocyte counts in ARIA+ cases. g, h Re-clustering of 65,481 T cells identifies canonical CD4⁺ (naïve, central/effector memory, Tregs) and CD8⁺ (naïve, central/effector memory, TEMRA, intermediate cytotoxic) states using concordant RNA and surface markers. i ARIA+ patients exhibit contraction of naïve CD8⁺ cells and enrichment of effector memory/TEMRA subsets. j Quantification of CD8 + TEM and TEMRA absolute cell counts from scRNAseq data. Individual samples show elevations in TEM (top) and TEMRA (bottom) numbers in ARIA+ patients (*p = 0.0234, Student’s two-tailed t-Test, squares = male, circles = female). Density plots k highlight TEMRA accumulation in ARIA+ only. l Differential expression (Fisher meta-analysis) in TEMRA cells from ARIA+ versus ARIA- reveals increased cytotoxic/Fc-receptor signaling, chemokine/migratory genes, MHC-II, inhibitory/stress markers, and metabolic regulators consistent with a glycolytic, glutamine-fueled effector state. Source data are provided as a Source Data file.
