Microglia Do Not Take Up Soluble Amyloid-beta Peptides, But Partially Degrade Them by Secreting Insulin-degrading Enzyme.

Neuroscience
Hongjun FuCynthia A Lemere

Abstract

Microglia play important roles in the pathogenesis of Alzheimer's disease (AD), in part, by affecting the clearance of amyloid-β (Aβ) peptides. Most studies, however, used synthetic soluble Aβ (sAβ) at higher concentrations. The exact mechanisms underlying microglia-mediated clearance of physiological sAβ at very low concentrations remain unclear. Here we reported that there were much more Iba-1- and CD68-positive microglia and significantly less sAβ left in the brain of adult mice 5 days after the surgery of sAβ microinjection compared to 2 h after the surgery (p < 0.05). However, very few Iba-1- and CD68-positive microglia co-localized with microinjected fluorescently labeled sAβ (FLsAβ42) 5 days after the surgery. Also, there was no co-localization of FLsAβ42 with a lysosomal marker (LAMP-1) 5 days after the surgery. There was no significant difference in the percentage of Aβ+/PE-CD11b+/APC-CD45low microglia between the control group and the group microinjected with TBS-soluble Aβ extracted from the brains of AD patients (p > 0.05). The degradation of physiological sAβ was prevented by a highly selective insulin-degrading enzyme inhibitor (Ii1) but not by a phagocytosis inhibitor (polyinosinic acid) or pinocytosis inhibitor ...Continue Reading

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