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Growing evidence has indicated that prefibrillar form of soluble amyloid beta (sAβ 1–42 ) is the major causative factor in the synaptic dysfunction associated with AD. The molecular changes leading to presynaptic dysfunction caused by sAβ 1–42 , however, still remains elusive. Recently, we found that sAβ 1–42  inhibits chemically induced long-term potentiation-induced synaptogenesis by suppressing the intersynaptic vesicle trafficking through calcium (Ca 2+ ) dependent hyperphosphorylation of synapsin and CaMKIV. However, it is still unclear how sAβ 1–42  increases intracellular Ca 2+  that induces hyperphosphorylation of CaMKIV and synapsin, and what is the functional consequences of sAβ 1–42 -induced defects in intersynaptic vesicle trafficking in physiological conditions. In this study, we showed that sAβ 1–42 elevated intracellular Ca 2+  through not only extracellular Ca 2+  influx but also Ca 2+  release from mitochondria. Surprisingly, without Ca 2+  release from mitochondria, sAβ 1–42  failed to increase intracellular Ca 2+  even in the presence of normal extracellular Ca 2+ . We further found that sAβ 1–42 -induced mitochondria Ca 2+  release alone sufficiently increased Serine 9 phosphorylation of synapsin. By blocking synaptic vesicle reallocation, sAβ 1–42  significantly increased heterogeneity of total synaptic vesicle pool size among synapses. Together, our results suggested that by disrupting the axonal vesicle trafficking, sAβ 1–42  disabled neurons to adjust synaptic pool sizes among synapses, which might prevent homeostatic rescaling in synaptic strength of individual neurons.   Electronic supplementary material  The online version of this article (10.1186/s13041-018-0353-z) contains supplementary material, which is available to authorized users.

Soluble Aβ1–42 increases the heterogeneity in synaptic vesicle pool size among synapses by suppressing intersynaptic vesicle sharing