The calcium hypothesis of neurodegenerative disorders such as Alzheimer's disease (AD) suggests that altered cytosolic Ca(2+) levels ( Ca(2+) (i)) and/or disturbances in Ca2+ homeostasis concern cellular mechanisms underlying neuronal pathology. To search for a diagnostic marker of Alzheimer's disease, we measured cytosolic calcium concentrations in platelets of AD patients, age-matched control subjects (AMC), and vascular dementia (VD) patients. The ( Ca(2+) (i)) was determined using long wavelength indicator Fluo-3AM in 21 mild AD patients, 17 AMC, and 23 patients with VD. The basal values of [Ca(2+)](i) were significantly lower in AD compared to AMC. After the addition of 1 mM calcium, the [Ca(2+)](i) markedly increased in platelets of AD compared to AMC and VD. Measurement of calcium homeostasis could provide a very sensitive, but less specific biological marker of AD. These results support the hypothesis that influencing calcium homeostasis may provide a therapeutic strategy in dementia.