Analysis of calcium homeostasis in fresh lymphocytes from patients with sporadic Alzheimer's disease or mild cognitive impairment

摘要

Alzheimer's disease (AD) is the most widespread, age-related neurodegenerative disorder. Its two subtypes are sporadic AD (SAD) of unknown etiology and genetically encoded familial AD (FAD). The onset of AD is often preceded by mild cognitive impairment (MCI). Calcium dynamics were found to be dysregulated in FAD models, but little is known about the features of calcium dynamics in SAD. To explore calcium homeostasis during the early stages of SAD, we investigated store-operated calcium entry (SOCE) and inositol triphosphate receptor (IP3R)-mediated calcium release into the cytoplasm in unmodified B lymphocytes from MCI and SAD patients and compared them with non-demented subjects (NDS). Calcium levels in the endoplasmic reticulum and both the rising and falling SOCE slopes were very similar in all three groups. However, we found that SAD and MCI cells were more prone to IP3R activation than NDS cells, and increases in calcium levels in the cytoplasm were almost twice as frequent in SAD cells than in NDS cells. MCI cells and SAD cells exhibited an enhanced magnitude of calcium influx during SOCE. MCI cells but not SAD cells were characterized by higher basal cellular calcium levels than NDS cells. In summary, perturbed calcium homeostasis was observed in peripheral cells from MCI and SAD patients. Thus, lymphocytes obtained from MCI subjects may be promising in the early diagnosis of individuals who will eventually develop SAD. However, no conclusions are made regarding SAD due to the limited number patients. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.