Fig 2: FIR light treatment ameliorated Aß deposition in the cortex and hippocampus. A Representative images of Aß (6E10) staining in the cerebral cortex and hippocampus from WT, APP/PS1 and FIR light-treated APP/PS1 mice. B Percentage of Aß plaque area in the cerebral cortex (n = 4). C Aß plaque density in the cerebral cortex (n = 4). D Percentage of Aß plaque area in the hippocampus (n = 4). E Aß plaque density in the hippocampus (n = 4). F The levels of Aß1-40 and Aß1-42 in the PBS fractions from the cerebral cortex (n = 5). G The levels of Aß1-40 and Aß1-42 in the guanidine hydrochloride fractions from the cerebral cortex (n = 5). Data were means ± SEM, *p < 0.05, **p < 0.01. ND: not detected

Fig 3: PCDH19 proteolytic cleavage is mediated by ADAM10 and possibly gamma secretase(A) Western blot of neurons treated with NMDA, MG132, and the proteases inhibitors GM6001, GI254023X, and DAPT, as indicated. Two different exposures are shown for PCDH19 FL, a short (short exp.) one and a long one.(B) Quantification of PCDH19 CTFs from neurons in (A). All CTF levels (CTF/FL) were increased by NMDA (n = 3–8, ***p < 0.001, Student's t test, CTRL compared with NMDA) and were significantly reduced by inhibitors of metalloproteases (n = 3–6; *p < 0.05, **p < 0.01, ***p < 0.001, Student’s t test, NMDA + GM6001 or NMDA + GI254023X compared with NMDA). Only the CTF3 level was reduced by the inhibitor of gamma secretase (n = 5–8; ***p < 0.001, Student’s t test, NMDA + DAPT compared with NMDA). Data are presented as mean ± SEM.(C) Representative western blot of neurons treated with NMDA and proteases inhibitors, as indicated. Two different exposures are shown for PCDH19 FL, a short (short exp.) one and a long one. Protease inhibitors were applied for 4 or 24 h before NMDA treatment (6 min).(D) Quantification of PCDH19 CTFs (CTFs/FL) from neurons in (C). All CTFs increased following NMDA treatment (n = 4–9; *p < 0.05, ***p < 0.001, Student’s t test, CTRL compared with NMDA). All CTFs decreased following 4 or 24 h of treatment with GI254023X (n = 4–6; **p < 0.01, ***p < 0.001, Student’s t test, NMDA + GI254023X compared with NMDA). The 4 h treatment with DAPT caused a decrease in CTF3 (n = 5; **p < 0.01, Student’s t test, NMDA + DAPT compared with NMDA). The 24 h treatment with DAPT caused an increase in CTF1 and CTF2 (n = 7–9; *p < 0.05, ***p < 0.001, Student’s t test, NMDA + DAPT compared with NMDA). Co-administration of GI254023X with DAPT reduced CTF3 levels at 4 h (n = 4; **p < 0.01, Student’s t test, NMDA + DAPT + GI254023X compared with NMDA) and prevented DAPT-mediated changes in CTF1 and CTF2 levels at 24 h. Data are presented as mean ± SEM.(E) Top panel, western blot of neurons treated with NMDA or NMDA + DAPT showing full-length presenilin-1 (PS1 FL) and presenilin-1 C-terminal fragment (PS1 CTF) expression. DAPT was applied for 4 or 24 h before NMDA treatment (6 min), as indicated. Bottom panel, quantification of PS1 FL and PS1 CTF. The 24 h treatment with DAPT caused a significant increase in PS1 CTF expression level (PS1 CTF/GAPDH, n = 3; **p < 0.01, ***p < 0.001, one-way ANOVA and Tukey’s post hoc test). Data are presented as mean ± SEM.(F) Scheme of PCDH19 proteolytic cleavage and resulting fragments (CTF1-3). GS, gamma secretase. Values are shown in Table S3.See also Figure S3 and Table S8.

Fig 4: FIR light ameliorated learning and memory deficit of AD mice. A Timeline of treatment with visible light (VIS), near infrared light (NIR) and far infrared light (FIR) on APP/PS1 mice. B Representative tracking routes of mice in training trials and spatial probe test. C The escape latency of mice to find the platform during training trials. D The number of entries in the zones around platform. E The mean swimming speed of mice. Data were means ± SEM, n = 5–8, *p < 0.05 compared to APP/PS1 mice without light treatment. N.S., not significant