LOW CEREBROSPINAL-FLUID CONCENTRATIONS OF PEPTIDE HISTIDINE VALINE AND SOMATOSTATIN-28 IN ALZHEIMERS-DISEASE - ALTERED PROCESSING OF PREPROVASOACTIVE INTESTINAL PEPTIDE AND PREPRO-SOMATOSTATIN

Recent studies have indicated that deposition of beta amyloid peptide in the brains of patients with senile dementia of the Alzheimer type ( SDAT) is a consequence of abnormal processing of the beta amyloid prot ein precursor. In addition, reduced concentrations of various peptides have been measured in post-mortem brain tissue and cerebrospinal flui d (CSF) of patients with SDAT. We determined concentrations of the pep tides derived from preprovasoactive intestinal peptide (VIP)- peptide histidine methionine-27 (PHM-27), peptide histidine valine (PHV) and V IP-and peptides derived from prepro-somatostatin (prepro-SS), SS-14 an d SS-28, in CSF of patients with SDAT by radioimmunoassay combined wit h high performance liquid chromatography. We found significantly reduc ed levels of total PHM-immunoreactivity (IR) and PHV, and unaltered le vels of PHM-27 and VIP in SDAT, compared with those in controls. Total SS-IR and SS-28 concentrations were significantly reduced in SDAT, wh ile SS-14 levels did not differ from those of controls. These results suggest that an altered processing of the prepro-peptides of VIP and S S may occur in SDAT and that these alterations might have a significan t role in the pathogenesis of SDAT.