Activation of the human supraoptic and paraventricular nucleus neurons with aging and in Alzheimer's disease as judged from increasing size of the Golgi apparatus.

The supraoptic (SON) and paraventricular nucleus (PVN) of the human hypothalamus produce vasopressin (AVP) and oxytocin (OXT). Since in these nuclei no cells are lost during aging or Alzheimer's Disease (AD), factors are searched for which may be responsible for this remarkable stability. Earlier work in both rat and human indicated that the peptide synthesis of these neurons was activated in the oldest age groups as judged from increased neuronal and nuclear size and AVP plasma levels. The size of the Golgi Apparatus (GA) has proved to be a very sensitive parameter for the synthetic activity of these neurosecretory cells in animal experiments. In order to determine changes in the GA during aging and in Alzheimer's Disease, we applied a polyclonal antiserum against immunoaffinity purified MG-160, a sialoglycoprotein of the medial cisternae of the GA, on formalin-fixed and paraffin-embedded sections of the SON and PVN of patients ranging in age from 29 to 97 years. However, our standard fixation procedure masked antigenic sites resulting in a minimal immunocytochemical staining in most of the tissues examined. It appeared to be possible, however, to retrieve the antigen and to obtain an excellent staining of the GA by heating sections in a microwave oven before immunostaining. Following this procedure, an increase in size and intensity of the GA became apparent in individuals from about 70 years and older. In AD patients a similar increase in size and intensity of the immunostained GA was observed. Taken together, these results indicate that SON and PVN neurons are activated during the course of aging and also in AD and that this activation takes place at an earlier age than observed previously by other cellular parameters.