ASTROGLIAL CONNEXIN IMMUNOREACTIVITY IS SPECIFICALLY ALTERED AT β-AMYLOID PLAQUES IN β-AMYLOID PRECURSOR PROTEIN/PRESENILIN1 MICE

Activation of astrocytes surrounding amyloid plaques is a hallmark of Alzheimer disease (AD) with consequences yet poorly understood. Astrocytes are characterized by a high level of intercellular communication mediated by two gap-junction forming proteins, connexin-43 and connexin-30. As astroglial connexins (Cxs) are involved in neuronal dysfunctions and death, we have analyzed their expression pattern in two murine models of AD, that is two different beta-amyloid precursor protein (APP)/presenilin1(PS1) mice, using western blot and immunohistochemistry analyzed in confocal microscopy. In young mice at 2 months, before the emergence of beta-amyloid (A beta) deposits, the distribution of both Cxs was similar to that of control mice. In older animals >= 4 months, local modifications in connexin immunostaining pattern were observed in the microenvironment of dense core A beta plaques. In a majority of plaques, an elevated immunoreactivity was detected for both Cxs contributing to the overall increase in connexin expression detected in 18 month old APP/PS1 mice. Activated microglial cells did not contribute to the elevated connexin immunoreactivity that was concentrated in astroglial processes infiltrating the plaques. In a small proportion of plaques (<= 15%) a depletion of immunoreactive connexin puncta was also found. As astroglial Cxs participate in neuroglial interactions, their remodeling may contribute to neuronal alterations observed at the periplaque area. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.