Marjanne Markerink

Age-related changes in concentrations of vasopressin in the central nervous system and plasma of the male wistar rat

The results of studies on the influence of age on concentrations of vasopressin (VP) in blood plasma and hypothalamic and extrahypothalamic brain sites have not been unequivocal. Studies on extrahypothalamic concentrations of VP in the aging rat have used two age groups only and have mainly provided semiquantitative data. For these reasons we determined, by radioimmunoassay, the concentrations of vasopressin in thirteen brain structures and in the plasma of 3-, 10-, 20- and 28-month-old male Wistar rats. Age-related decreases in VP concentrations were found in the pituitary gland, hypothalamus, thalamus, midbrain, medulla oblongata, amygdala and pineal gland, while an increase was noted in plasma. Decreases in the concentration of VP in the amygdala and pineal gland occurred between 3 and 10 months of age and probably represent developmental changes. In the pituitary, thalamus, midbrain, medulla oblongata and plasma, differences in the concentration of VP were also found between 10-month-old and older animals and are probably related to aging. The finding of increased plasma VP concentrations in aged animals agrees with the notion that neuronal function does not necessarily decline with age and suggests that neurons may even be activated. Age-related changes in VP concentrations were not observed in the other structures examined. It has been reported that the VP innervation of a number of brain structures depends on testosterone. Despite reports to the contrary VP concentrations do not generally decline in these structures with aging.

Peptidases Are Affected Differently in Neocortical Regions of Brains from Patients with Alzheimer's Disease

Although it is recognized that changes in protease activities may be involved in the etiology of pathological changes in the human brain, there have been few studies on normal and pathological protein

Reduced phosphatidylinositol kinase activity in Alzheimer's disease: effects of age and onset

Phosphatidylinositol kinase (PI kinase) and phosphatidylinositol phosphate kinase (PIP kinase) were assayed in a membrane-free cytosolic fraction prepared from the medial temporal cortex of patients with Alzheimers disease (AD) and nondemented controls, with exogenous lipids as substrate. 32P-PIP formation appeared to be reduced by 21% in patients with AD who died before 80 years, compared to matched controls. In addition, there was an age-related decrease in PI kinase activity in the control group. In the AD patients there was no age-related decrease. Very old AD patients (older than 80 when they died) with a short duration of the disease were characterized by increased PI kinase activity. No differences were found in the closely related enzyme PIP kinase. The results are indicative for heterogeneity in AD.

Platelet Phosphatidylinositol Kinase Activity Is Not Altered in Alzheimer Disease

We previously reported a specific decline in phosphatidylinositol (PI) kinase activity in the neocortex of patients with Alzheimer disease (AD) as compared to controls, whereas phosphatidylinositol phosphate (PIP) kinase activity appeared not to be affected (Jolles et al., 1992). In search of a possible systemic effect of AD, in the present study we investigated phosphoinositide kinase activity in platelets from patients with AD and from control subjects. The study was based on the notion that disease-specific abnormalities in the brain could be reflected in blood platelets. PI kinase activity was studied in platelet homogenates and in a salt-solubilized protein fraction of platelets, because of the difference in subcellular localization of the different types of PI kinases. In addition, NADH cytochrome-C reductase was measured in platelet homogenates as a marker for the endoplasmic reticulum, to detect a possible proliferation of the endoplasmic reticulum. AD patients and normal elderly controls showed no difference in PI kinase activity in either enzyme fraction. Furthermore, NADH cytochrome-C reductase activity and the protein/phospholipid ratio per 10(6) platelets were the same for AD patients and controls. This was taken as an indication that platelets in AD patients do not show proliferation of intracellular membranes.