Platelet phosphatidylinositol kinase activity is not altered in Alzheimer disease

Abstract

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.

Phosphoinositide metabolism, aging and Alzheimer's disease

“…Therefore, a decrease in the activity of this type of PI kinase could be closely related to the cellular pathology of AD, as neurofibrillary tangles are partially composed of incorrectly metabolized cytoskeletal components. Despite the indication that, firstly, disease-specific abnormalities in the brain, such as those occurring in diseases like Parkinson's disease, Huntington's disease and depression, can be reflected in blood platelets [151], and secondly, PI kinase activity is substantially decreased in the cortex of AD brains, PI kinase activity in platelets from AD patients was not different from that of control platelets [152,153].…”