A novel membrane protein, encoded by the gene covering KIAA0233, is transcriptionally induced in senile plaque-associated astrocytes

Abstract

Beta-amyloid (Aβ) deposition and senile plaque-associated astrocytes are common neuropathological features of Alzheimer's disease (AD). Although the molecular mechanisms by which Aβ contributes to the progression of neuropathologic changes have not been entirely established, there is little doubt that the association of Aβ with astrocytes, the predominant cell type in brain, significantly influences exacerbation of the disease. In an effort to identify astrocyte-derived molecules that may be intimately associated with progression of AD, we identified a novel Aβ-induced rat gene, designated Mib, whose human counterpart covers KIAA0233. Mib-transfected C6 cells express Mib protein in the endoplasmic reticulum and endplasmic reticulum–Golgi-intermediate compartment. To evaluate roles of Mib in AD, we investigated its expression in the AD brain. In non-AD brains, Mib mRNA has been detected in neurons but not in quiescent astrocytes. On the contrary, in AD brains, Mib mRNA is expressed in activated astrocytes associated with senile plaques, but not expressed in neurons around lesions. From these observations, Mib appears to be a novel Aβ-responsive gene that may play a role in astrocyte inflammatory activation around senile plaques in the AD brain.