The calcium hypothesis of neurodegenerative disorders such as Alzheimer´s disease (AD) suggests that altered cytosolic Ca2+ levels ([Ca2+]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 ([Ca2+]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 [Ca2+]i were significantly lower in AD compared to AMC. After the addition of 1 mM calcium, the [Ca2+]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.
We investigated the role of serotonin in cognitive activation of the frontal cortex. The serotonergic system was affected by the administration of an amino acids mixture without tryptophan (tryptophan depletion). In a placebo-controlled double-blind cross-over study with 20 healthy volunteers, we tested the hypothesis that a tryptophan (serotonin)
decrease affects the activation of prefrontal cortex by the Stroop test. Cognitive brain activation was evaluated by functional magnetic resonance imaging (fMRI). Tryptophan depletion decreased the plasma tryptophan level up to 90 % for five hours after the tryptophan-free drink had been consumed when compared with the same mixture with tryptophan (p ≤
0.0001). Tryptophan depletion did not affect the Stroop test performance. We compared fMRI activation in both conditions (tryptophan depletion and placebo) with plasma tryptophan levels as the covariates. The tryptophan
depletion increased the activation (fMRI signal) in the bilateral mediofrontal cortex, anterior cingulate and left dorsolateral prefrontal cortex. The present findings allow the postulate that serotonergic medial forebrain and cingulum bundle pathways play a role in the activity of cortical structures involved in Stroop test processing.