Single Point Mutation from E22-to-K in Aβ Initiates Early-Onset Alzheimer’s Disease by Binding with Catalase

Figure 7

E22K induced stronger cell toxicity by eliciting intracellular Ca²⁺ influx [Ca²⁺]i in cultured N2a cells and more rapid memory decline than Aβ in SD rats. (a–d) The effects of saline (Con), Aβ, Aβ plus H₂O₂, E22K, and E22K plus H₂O₂ on intracellular Ca²⁺ levels by confocal microscopy (: number of independent cell culture preparations). (e–g) The effects of saline (Con), Aβ, Aβ plus L-cys, E22K, and E22K plus L-cys on cellular toxicity using a CCK-8 kit (: number of independent cell culture preparations). (h) The model of Aβ or E22K-induced neurotoxicity. Briefly, Aβ or E22K can enter into mitochondria and bind with catalase to induce H₂O₂ accumulation; in turn, H₂O₂ with Aβ or E22K acts to synergistically increase [Ca²⁺]i and to induce neuronal death (: number of independent cell culture preparations). . Data are . (i) No difference in swimming speed among the five groups tested (saline (Con), Aβ, Aβ plus L-cys, E22K, and E22K plus L-cys) was observed in Morris water maze (MWM, above). (j) Escape latencies in the MWM. (k, l) Representative numbers of platform crossings (k, swimming trace, above) and (l) time spent in the target quadrant on day 7 (: number of rats). . Data are .

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