Fig. 1

The boxplot compares the AAO in patients carrying autosomal dominant variants (a.d., n = 7), APOE4/4 carriers (n = 5), established risk variants (n = 16) and those without established variants (n = 32). Significantly earlier onset was found in the a.d. group compared to the risk variant (p = 0.003) and no variant (p = 0.002) group. Note that the difference to APOE4 homozygote carriers was statistically not significant (p = 0.385). Significance was lost when correcting for multiple testing comparing APOE4/4 carriers to patients carrying risk variants (p = 0.036, adj. p = 0.138) and to patients with no variant (p = 0.048, adj.p = 0.138) No difference was found between carriers of risk variants) compared to the rest of the cohort (p = 0.849). Statistical analysis was performed using Mann–Whitney U test and corrected for multiple testing using the Holm-Sidak method; boxplots represent median, quartiles and outliers according to the Tukey method; a.d. = autosomal dominant variants in PSEN1, MAPT, APP, GRN; APOE4/4 = APOE4 homozygote carriers; risk variant = patients with established risk variants, including TREM2 p.(R417H) and APOE4 heterozygotes; no variant = patients with no established risk variants nor variants in established risk genes (including patients with potential new risk variants and new candidate gene variants for dementia). Note that one patient, EOD-2, who carries two established risk variants (heterozygous APOE4 and TREM2 p.(R62C) and one autosomal dominant variant MAPT p.(P636L), was only assigned to the group of autosomal dominant carriers