Neuroendocrine-specific protein C, a marker of neuronal differentiation, is reduced in brain of patients with Down syndrome and Alzheimer's disease

Neuroendocrine-specific protein C (NSP-C) is found in neural and neuroendoc rine cells and associated with the endoplasmic reticulum, Its expression wa s found to correlate with the degree of neuronal differentiation. As the ne uropathological findings in Down syndrome (DS) includes deficits of differe ntiation, and we detected a downregulated sequence with 100% homology with NSP-C homolog mRNA in temporal cortex of patients with DS as well as Alzhei mer's disease (AD) using differential display-polymerase chain reaction (DD -PCR), we decided to examine the protein levels of NSP-C in temporal, front al cortex and cerebellum of DS and AD. To normalize NSP-C versus neuronal d ensity, we also determined neuron-specific enolase (NSE) levels and calcula ted the ratios. NSP-C was significantly reduced in DS (temporal and frontal cortex) and AD (frontal cortex) compared to controls. The significant decr ease of NSP-C in DS was even more pronounced when related to NSE levels. Im paired differentiation in DS brain may well be due to absolutely and relati vely decreased NSP-C levels in temporal and frontal cortex. As NSP-C was al so reduced in AD frontal cortex, NSP-C deficits in these disorders may be r eflecting neurodegenerative changes rather than a primary and specific find ing of DS or AD pathogenesis, (C) 2000 Academic Press.