Differential display reveals downregulation of the phospholipid transfer protein (PLTP) at the mRNA level in brains of patients with Down syndrome

The phospholipid transfer protein (PLTP) shows a wide variety of functions including transfer of phospholipids and other lipid-like substances. Perfor ming gene hunting in brain of patients with Down syndrome (DS) we detected the absence of a fragment identified as PLTP. Cerebellum of 4 controls, 7 p atients with DS, 5 patients with Alzheimer's disease (AD) were used for dif ferential display and for quantification of mRNA steady state levels of the isomer PLTP-1 by blotting methods. Differential display showed the absence of a cDNA fragment and cloning, sequencing and gene bank work revealed 100 % homology with human PAC 337018 on chromosome 20q containing the PLTP gene . The PLTP gene in turn consists of at least three different PLTP isomers. Based on these results, a 450 bp cDNA fragment of the PLTP-isomer I (PLTP I ) was isolated and amplified by PCR, serving as probe for the PLTP-1 isomer and its expression level was found to be significantly reduced in cerebell um of patients with DS. Biologically, the downregulation of PLTP maybe invo lved in the pathology of DS as phospholipids not only are of importance for membrane biogenesis and structure but also in the regulation of cellular m etabolism, signaling and growth. In the brain, phospholipids in addition ar e integral constituents of myelins and synaptosomes (Johnson etc) and defic ient PLTP levels may account for the deteriorated functions described to oc cur in DS brain. (C) 2001 Elsevier Science Inc. All rights reserved.