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 Alzheimer''s 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.