Pathogenesis of Alzheimer's disease: Involvement of the choroid plexus.

The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which in aging and Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions of the involved tissues, the CSF abnormalities reported in these conditions are suggestive of ChP injury. Indeed, several studies document ChP damage in aging and AD, which nevertheless remains to be systematically characterized. We here report that the changes elicited in the CSF by AD are consistent with a perturbed aging process and accompanied by aberrant accumulation of inflammatory signals and metabolically active proteins in the ChP. Magnetic resonance imaging (MRI) imaging shows that these molecular aberrancies correspond to significant remodeling of ChP in AD, which correlates with aging and cognitive decline. Collectively, our preliminary post-mortem and in vivo findings reveal a repertoire of ChP pathologies indicative of its dysfunction and involvement in the pathogenesis of AD. HIGHLIGHTS: Cerebrospinal fluid changes associated with aging are perturbed in Alzheimer's disease Paradoxically, in Alzheimer's disease, the choroid plexus exhibits increased cytokine levels without evidence of inflammatory activation or infiltrates In Alzheimer's disease, increased choroid plexus volumes correlate with age and cognitive performance.

Application of brush cytology for FISH-based detection of 1p/19q codeletion in oligodendroglial tumors.

Currently, oligodendroglial tumours (OT) are routinely tested for 1p/19q codeletion, a genetic abnormality of prognostic value. This analysis is most commonly performed by fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin embedded (FFPE) tissue sections, which is time-consuming and often difficult to interpret, mainly due to the presence of truncated and overlapping nuclei. To overcome these methodological disadvantages, we investigated the validity of cytospins prepared from brushings of fresh tissue samples for assessing 1p/19q status by FISH. For this purpose, FISH analysis of 1p/19q codeletion was performed on FFPE tissue sections and cytospins prepared from brushing of corresponding fresh tissue in a series of 35 central nervous system tumours (16 OT and 19 non-OT). An aberrant 1p/19q status was found in 11/16 (69 %) OT samples and included codeletion of 1p/19q (7), 1p/19q imbalance (2) isolated 19q deletion (1) and 1p imbalance (1). None of the 19 non-OT samples showed 1p/19q codeletion. Results of FISH were concordant between FFPE sections and cytospins in all cases in which both types of slides gave interpretable results. Interpretation of FISH signals on cytospins was easier and quicker than on FFPE sections. Our study showed that cytospins prepared from brushing of fresh tissue samples allow quick and reliable FISH based analysis of 1p/19q status and can substitute traditional FFPE sections when fresh tissue is available.