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. 2024 Apr 24;19:38. doi: 10.1186/s13024-024-00726-8

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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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