Decreased brain levels of 2 ',3 '-cyclic nucleotide-3 '-phosphodiesterase in Down syndrome and Alzheimer's disease

In Down syndrome (DS) as well as in Alzheimer's disease (AD) oligodendrogli al and myelin alterations have been reported. 2-',3'-cyclic nucleotide-3'-p hosphodiesterase: (CNPase) and carbonic anhydrase II (CA II) are widely acc epted as markers for oligodendroglia and myelin. However, only data on CNPa se activity have been available in AD and DS brains so far. In our study we determined the protein levels of CNPase and CA II in DS, AD and in control post mortem brain samples in order to assess oligodendroglia and myelin al terations in both diseases. We used two dimensional electrophoresis to sepa rate brain proteins that were subsequently identified by matrix assisted la ser desorption and ionization mass-spectroscopy (MALDI-MS). Seven brain are as were investigated frontal, temporal, occipital and parietal cortex, cere bellum, thalamus and caudate nucleus). In comparison to control brains we d etected significantly decreased CNPase protein levels in frontal and tempor al cortex of DS patients. The level of CA II protein in DS was unchanged in comparison to controls. in AD brains levels of CNPase were decreased in fr ontal cortex only. The level of CA II in all brain areas in AD group was co mparable to controls. Changes of CNPase protein levels in DS and AD are in agreement with the previous finding of decreased CNPase activity in DS and AD brain. They probably reflect decreased oligodendroglial density and/or r educed myelination. These can be secondary to disturbances in axon/oligoden droglial communication due to neuronal loss present in both diseases. Alter natively, reduced CNPase levels in DS brains may be caused by impairment of glucose metabolism and/or alterations of thyroid functions. (C) 2001 Elsev ier Science Inc. All rights reserved.