Fig. 1: Age-dependent biomarker changes in APPPS1 mice and experimental group design.

a Normalized absolute changes (%) in brain Aβ levels, brain Aβ seeding activity (SD₅₀), and CSF NfL as a function of age in APPPS1 mice. Data were largely taken from previous publications (for brain Aβ measured by immunoassays¹³; for in vivo Aβ seeding activity (Reed-Muench method)¹³; for CSF NfL¹¹ and from in-house mouse bio-/databank (see Supplementary Table 1; note that, from each of the NfL values of APPPS1 mice, the mean of the NfL values of age-matched wild-type mice was subtracted since wild-type mice also show an age-related increase⁵⁹). Means and ± s.e.m. are shown and curves were generated in Numbers (Apple Inc., Cupertino, CA) using the “curved connection line” option. Results reveal a steady increase in brain Aβ until it slows down at a late age, whereas Aβ seeding activity increases more rapidly and reaches a plateau as early as ~12-mo of age (see also Fig. 3c where log SD₅₀ data are plotted using the curve-fitting method). CSF NfL increases slowly until ~10–11-mo of age, after which a more rapid increase takes place. b Experimental treatment groups cover distinct time-points of decisive biomarker changes. Mice were treated either with BACE1 inhibitor- (BI) containing food pellets (red) or control (Ctrl) food pellets (gray). Three-month treatment periods (short-term) started when animals were 1.5 (young), 12 (adult), or 18.5 (aged) mo of age, and mice were analyzed at the end of each 3-month treatment period (dots). To assess baseline levels (Bsl), untreated mice were also collected at 1.5, 12, and 18.5 mo of age (dots). Chronic BI treatments (blue) started at 1.5 or 12 months of age and lasted until 21.5 months (young-chronic and adult-chronic, respectively) when the animals were sacrificed. Chronic BI treatments were also administered to control wildtype (WT) mice. Number of mice per group was n = 9–16; for exact numbers see Supplementary Fig. 1a.