The phospholipid transfer protein (PLTP) shows a wide variety of functions including transfer of phospholipids and other lipid-like substances. Performing 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 patients with DS, 5 patients with Alzheimer's disease (AD) were used for differential 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 cerebellum of patients with DS. Biologically, the downregulation of PLTP maybe involved in the pathology of DS as phospholipids not only are of importance for membrane biogenesis and structure but also in the regulation of cellular metabolism, signaling and growth. In the brain, phospholipids in addition are integral constituents of myelins and synaptosomes (Johnson etc) and deficient PLTP levels may account for the deteriorated functions described to occur in DS brain.