Low cerebrospinal fluid concentrations of peptide histidine valine and somatostatin-28 in Alzheimer's disease: altered processing of prepro-vasoactive intestinal peptide and prepro-somatostatin.

摘要

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 protein precursor. In addition, reduced concentrations of various peptides have been measured in post-mortem brain tissue and cerebrospinal fluid (CSF) of patients with SDAT. We determined concentrations of the peptides derived from prepro-vasoactive intestinal peptide (VIP)--peptide histidine methionine-27 (PHM-27), peptide histidine valine (PHV) and VIP--and peptides derived from prepro-somatostatin (prepro-SS), SS-14 and SS-28, in CSF of patients with SDAT by radioimmunoassay combined with high performance liquid chromatography. We found significantly reduced levels of total PHM-immunoreactivity (IR) and PHV, and unaltered levels of PHM-27 and VIP in SDAT, compared with those in controls. Total SS-IR and SS-28 concentrations were significantly reduced in SDAT, while SS-14 levels did not differ from those of controls. These results suggest that an altered processing of the prepro-peptides of VIP and SS may occur in SDAT and that these alterations might have a significant role in the pathogenesis of SDAT.