Figure 2. Changes in CSF PGRN as a function of EYO.

1. CSF PGRN as a function of EYO in mutation carriers (MC, red) and non‐carriers (NC, blue). The solid lines indicate the regression line for each of the groups and the 95% confidence interval (CI) calculated by a linear model adjusting by gender. The interaction term of mutation status and EYO is significant (P = 0.041), also when including PGRN outliers and participants with EYO > +20 (P = 0.030). Individual data points are not displayed to prevent disclosure of mutation status.
2. The graph depicts the standardized differences in CSF PGRN between MCs and NCs as a function of EYO, in the context of other biomarker and cognitive changes. The curves were generated by the linear model that best fit each marker (see Statistical analysis section and Appendix Table S2). CSF PGRN is significantly increased in MC compared to NC 10 years before the expected symptom onset (shadowed area) after brain amyloidosis and brain injury (as measured by CSF T‐tau) have started, and shortly before CSF sTREM2 starts to increase.

Data information: Aβ_1–42: amyloid‐β 42; CSF, cerebrospinal fluid; MC, mutation carrier; MMSE, Mini‐Mental State Examination; NC, non‐carrier; T‐tau, total tau.