Fig. 2

TNAP haploinsufficiency prevents the development of amyloid plaques in APP/PS1^+/− mice. (A) Representative confocal microscopy images of senile plaques (APP red channel) in the hippocampus of APP/PS1^+/− and APP/PS1^+/−/TNAP^+/− mice. Nuclei were stained with DAPI. Scale bar: 500 μm. (B, C) Graphs represent the distribution of values per group (median, IQR, maximum, and minimum values) of the number (B) and the percentage of area (C) of hippocampal senile plaques. When indicated, black square data points represent males and open square data points represent females. (D) Representative immunoblot of APP and fragments C99 and C83 in homogenates from the hippocampus of APP/PS1^+/− and APP/PS1^+/−/TNAP^+/− mice. (E-H) Quantification of C99/APP (E), C83/APP (F), C99/C83 (G), and APP (H) protein levels in the hippocampus of APP/PS1^+/− (n = 10 or 11) and APP/PS1^+/−/TNAP^+/− (n = 8) mice. Levels of α-tubulin were used as loading control for normalization purposes. Data are given as a percentage relative to APP/PS1^+/− mice, and graphs show the distribution of values per group (median, IQR, maximum, and minimum values). I-K. Representative confocal microscopy images showing TNAP punctate pattern (green channel) in senile plaques (WO2, red channel) (I) and TNAP in microglial cells (Iba-1, green channel) (J), both in the hippocampus of APP/PS1^+/− mice. Samples from Alzheimer´s disease patients mimic the TNAP punctate pattern (green channel) in hippocampal senile plaques (WO2, red channel) (K) Nuclei were stained with DAPI. Scale bar: 20 μm. Data in box plots represent median ± SD. * P ≤ 0.05 or ** P ≤ 0.01; using an unpaired two-tailed Student’s t-test