Experimental design

WT and G2019S mice were exposed to intraperitoneal (ip) injections of a low dose of lipopolysaccharide LPS (0,1 mg kg^-1 Escherichia coli serotype O111:B4) (Sigma-Aldrich), administrated twice a week for 12 weeks ( Supplementary Figure 1 ). Treatments were performed in two different age groups, 3M (young adult) and 7M (at the start of middle-age). WT and G2019S mice exposed to ip injections of 0.9% sterile NaCl were used as controls.

Young mice receiving the treatment for 12 weeks were sacrificed at 6 M; middle aged mice were subdivided in 2 groups; one group received the treatment for 12 weeks was killed at 10 M, the second group received the treatment for 12 weeks and from 10 M to 16 M received saline only ( Supplementary Figure 1A-B ).

Mice (n = 20/experimental group) were randomly assigned to one of seven experimental conditions for each genotype:

1 . 3 M Basal (no injections);

2 . 6 M NaCl (NaCl injections started at 3 M);

3 . 6 M LPS (LPS injections started at 3 M);

4 .10 M NaCl (NaCl injections started at 7 M);

5 .10 M LPS (injections started at 7M);

6 . 16 M NaCl (injections started at 7 M);

7. 16 M LPS (injections started at 7 M).

Clinical evaluation (body weight, mantel status, lethargy, reluctance to move, grooming behavior) was carried out weekly until sacrifice.

A second series of experiments were carried out (n=8 mice/experimental group) for immunohistochemical and protein analyses.