P1-148: Altered Reelin expression in Alzheimer’s disease brain and cerebrospinal fluid

Abstract

Reelin is a glycoprotein that is essential for the correct cytoarchitectonic organization of the developing CNS. Its function in the adult brain is less understood, although it has been proposed that Reelin is involved in signalling pathways linked to neurodegeneration. We have recently reported the presence of Reelin protein in cerebrospinal fluid (CSF) and demonstrated elevated levels of a 180 kDa Reelin fragment in patients affected by Alzheimer's disease (AD). To confirm these findings, here we analyzed Reelin expression in brains and CSF from AD patients and non–demented controls (NDC). Reelin immunoreactivity pattern was analyzed in CSF by SDS–PAGE and Western blot. To determine whether changes in CSF Reelin reflect differences in brain levels of this protein, we examined the expression of Reelin in tissue samples from the frontal cortex and cerebellum frontal (from same cases) of AD and NDC cases, by Western blot analysis and semi–quantitative PCR assay. We found a 40% increase in the Reelin protein levels in the frontal cortex of AD patients compared to controls. Similar increases were detected at the Reelin mRNA transcriptional level. Next, we examined whether CSF Reelin levels were also altered in neurological diseases, including frontotemporal dementia, progressive supranuclear palsy and Parkinson's disease, in addition to AD. The Reelin 180 kDa band increased in all the neurodegenerative disorders analysed. Taken together, our results show that Reelin is up–regulated in the brain and CSF in several neurodegenerative diseases, thereby supporting the notion that Reelin is involved in the pathogenesis of a number of neurodegenerative diseases.