Fig. 1

Peripheral CD8⁺ TEMRA cells accumulate in AD patients before the onset of dementia. a Cohort demographics. b Experimental overview c. Heatmap showing median expression values of selected markers for the major immune cell populations. d UMAPs displaying pre-gated T cells, B cells and DCs, monocytes and NK cells from the blood of control and AD cases. Colors correspond to PARC-guided clustering. e Heatmap showing the top 25 populations with differential abundance between groups measured by ANOVA. f Violin plots displaying the percentage of significant different immune cell subsets out of the total CD45⁺ immune population using a GLM with age and sex as covariates. g Stacked bar graphs showing the percentage of CD4⁺ and CD8⁺ T cell subpopulations of total CD4⁺ T cells and CD8⁺ T cells using a GLM with age and sex as covariates. h Pie charts showing the percentage of CD8⁺ TEMRA subpopulations of total CD8⁺ TEMRA cells. i Correlation graph showing the association between PD1 expression on CD8⁺ TEMRA cells and CSF-derived Aβ42 (left) and pTau181 (right) levels using a Spearman's rho correlation with age/sex correction in the entire cohort. j Violin plots displaying the percentage of significant different T cell subsets out of the total CD45⁺ immune population using a GLM with age and sex as covariates between Aβ-negative and –positive patients with MCI. k Correlation graph showing the association between effector CD8⁺ T cells and CSF-derived Aβ42 levels using a Spearman's rho correlation with age/sex correction. f, j Violin plots show median ± quartiles. i, k Correlation plot show linear regression ± 95% confidence intervals; a-k. n = 115 in total, n = 35 of control, n = 21 of MCI due to AD, n = 59 of Dem, n = 16 Aβ⁻ MCI spectrum, n = 25 Aβ⁺ MCI spectrum; 3,204,588 CD3⁺ T cells, 3,168,876 DCs, monocytes & NK cells and 2,288,834 CD19⁺ B cells were imputed in the clustering analyses; GLM = multivariate general linear model; Ctrl = Control, MCI = mild cognitive impairment; Dem = ; AD = Alzheimer’s disease; TEMRA = terminally differentiated effector memory cells re-expressing CD45RA; DCs = dendritic cells; γδ = gamma-delta; NK = natural-killer