Fig. 10

Schematic depiction of PRDX6 dependent mechanisms in Aβ homeostasis: a and b preventive effect on nascent plaque seeding and c and d remodeling of mature plaques. a Overexpression of Prdx6 is associated with reduced number of nascent plaques and specifically those, which are devoid of activated astrocytes and/or microglia cells. b In contrast, Prdx6 haplodeficiency increases number of nascent plaques including those, which are not associated with astro- and micro- glial cells. c Mature plaques in Prdx6 overexpressing mice show increased plaque compactness and diminished deposition of diffuse Aβ peptide around the plaque fibrillar core. d Conversely, Prdx6 haplodeficiency is associated with reduced plaque compactness and increased amount of diffuse Aβ in the plaque periphery. There is a direct association between the Prdx6 gene dose and periplaque activation of astrocytes and microglia. Since PRDX6 is an astrocytic protein these observations imply phagocytic function of microglia in Aβ proteostasis is regulated by astrocytes