a, The top individual clones in AD were assessed by combining scRNA-seq and scTCR-seq datasets. A MAST differential expression test with Benjamini–Hochberg correction was conducted to compare CD8+ T cell maximum clones (n = 12–18 cells) from patients with MCI or AD against all CSF T cells. Note the colocalization of AD clones with CD8+ clusters on the t-SNE plots. b, Separate analysis of patients with MCI, AD and PD by percentages of maximum clones revealed an enrichment of highly expanded clones (defined as comprising 3% or more of all TCRαβ sequences; indicated by dotted line) in patients with these diseases. Only one out of ten healthy subjects had a highly expanded clone in their CSF, versus four out of six patients with AD, two out of six patients with PD and one out of five patients with MCI. c, Quantification of overall clonality (defined as the percentage of total TCRαβ sequences that are identical to one or more TCRαβ sequences) in the four groups of cohort 4. Significance was measured by two-way ANOVA followed by Tukey’s multiple comparisons test. Only samples with detectable clones were included in the analysis (n = 11 healthy; n = 5 MCI; n = 5 AD; n = 6 PD). Box plots in b, c Box plots show median and 25th to 75th percentiles, and whiskers indicate the minimum and maximum values. d, Gene-expression analysis was conducted on all 24 samples and clustered by t-SNE. Clusters were composed of a mixture of groups, patients, clonal and non-clonal cells. e, Genes (encoding cytotoxic effector proteins) that showed increased expression in a maximum PD clone (n = 14 cells) were analogous to those observed to be overexpressed in AD clones. MAST differential expression test with Benjamini–Hochberg correction. Source data