BRAIN VASOPRESSIN LEVELS IN DOWN-SYNDROME AND ALZHEIMERS-DISEASE

Performing gene hunting in Down Syndrome fetal brain we detected an ov erexpressed sequence highly homologous to the human vasopressin gene. As this neuropeptide may be involved in the pathogenetic mechanism and , moreover, was described to play a role in memory and learning, we de cided to study the brain gene product level in Down Syndrome (DS), con trols and patients with Alzheimer's disease (AD). Subtractive hybridiz ation was used to study the differential expression between steady sta te mRNA levels in fetal brain of DS and controls at the 23rd week of g estation. A radioimmunological method was used to determine vasopressi n (AVP) in five brain regions of each 9 aged DS brains, 9 brains with AD and 9 control individuals, obtained from brain bank. An overexpress ed nucleic acid sequence with 91% homology to the vasopressin gene was detected in both fetal brains with DS, AVP levels in controls were of the order cerebellum > occipital > frontal > parietal > temporal lobe and were significantly higher in temporal lobe and lower in cerebellu m of patients with DS. AVP levels in brain of AD patients were also si gnificantly increased in temporal lobe but were not reduced in cerebel lum. The biological meaning of increased AVP remain unclear but may be linked to the neurodegenerative processes, proposed to be similar in both disorders. Data from gene hunting in fetal DS brain along with ou r data on aged DS and AD patients suggest the early involvement of AVP in the pathomechanism accompanying cholinergic, monoaminergic and neu ropeptidergic deficits described in DS and AD. (C) 1998 Elsevier Scien ce B.V. All rights reserved.