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- W2980387632 abstract "Previously, we reported that ILEI (also referred to as FAM3C) binds to the γ–secretase complex and suppresses amyloid–β peptide (Aβ) production by destabilizing the precursor APP–C99 without inhibiting γ–secretase activity. Neuronal ILEI resides in the trans–Golgi network and presynaptic terminal. Synaptosome fractionation analysis further indicated that ILEI is colocalized with APP and the γ–secretase complex at the active zone–docked synaptic vesicles. In this study, we investigated the relationship between ILEI release and synaptic activity. We generated monoclonal antibodies against recombinant ILEI and setup sandwich ELISA for mouse ILEI. Using the established ELISA, we measured ILEI in brain soluble fractions and cerebrospinal fluid (CSF). We also applied microdialysis to monitor ILEI and Aβ concentrations in the interstitial fluid of cerebral cortex of freely moving humanized mutant APP–knockin mice. Soluble fractions of brain homogenates contain a secreted form of ILEI. Three mice in a same cage were sacrificed every 3 hours for a day. Brain ILEI level showed phasic alteration; low in daytime and high in nighttime. Fluctuation of CSF ILEI was not synchronized with that of brain ILEI. Microdialysis study using APP–knockin mice revealed that interstitial fluid concentration of ILEI was roughly parallel with a level of physical activity (amount of movement) but not always with that of Aβ. Treatment with anesthetics, tetrodotoxin or tetanus toxid obviously decreased both of ILEI and Aβ in the interstitial fluid. Our results suggested that presynaptic ILEI and Aβ were similarly released into the extracellular space in a synaptic activity–dependent manner." @default.
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- W2980387632 date "2019-07-01" @default.
- W2980387632 modified "2023-10-16" @default.
- W2980387632 title "P1-163: SYNAPTIC ACTIVITY-DEPENDENT RELEASE OF PRESYNAPTIC ILEI/FAM3C" @default.
- W2980387632 doi "https://doi.org/10.1016/j.jalz.2019.06.718" @default.
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