Fig. 3

Soluble Aβ oligomers increase oxidative stress in mitochondria in neurons in vivo. a Experimental procedure to determine the effects of Aβo on mitochondrial oxidative stress in the healthy mouse brain in vivo. 4-mo-old C57Bl/6 mice were injected with AAV.hSyn.mt-roGFP and a cranial window was implanted 3 weeks later. Oxidative stress in mitochondria was assessed by two photon microscopy in basal conditions and after topical application of either WtCM, TgCM or Aβ-immunodepleted TgCM. b Representative pictures of the effects of CM in neuronal mitochondria in the Wt mouse brain. Scale bar represents 20 μm and 5 μm in the insets. Only TgCM was able to increase oxidative stress levels. c—e Graphs show histograms of mitochondrial oxidative stress frequency distribution (Ratio 800/900) for the three conditions before (basal) and after application of CM in neurons. f Averaged 800/900 ratios before and after CM treatment for each z-stack acquired. Darker traces represent z-stacks showing an increase ≥ 25% in Ratio 800/900 after topical application of CM. g Scatter dot plot represents the relative change (ΔR/Ro) in ratio for each condition. Error bars represent mean ± SEM (WtCM: 5.90 ± 2.534%, n = 21 z-stacks; TgCM: 32.50 ± 3.328%, 24 z-stacks; depleted TgCM: 13.20 ± 4.340%, 24 z-stacks from 4, 4 and 5 mice respectively (all male), **p < 0.01, ****p < 0.0001)