Altered Ca2+ homeostasis in lymphoblasts from patients with late-onset Alzheimer disease.

The authors report calcium (Ca2+) homeostasis features of transformed lymphocytes from patients with late-onset Alzheimer disease and healthy age-matched controls. Alzheimer lymphoblasts show higher basal cytosolic-free [Ca2+] than controls. The antibodies anti-immunoglobulin M or the beta-amyloid (beta-amyloid) peptide fragment 25-35-induced elevation of cytosolic-free [Ca2+] was higher in Alzheimer disease lymphoblasts than in control cells. However, the kinetics of Ca2+ replenishment of Ca(2+)-depleted cells shows a higher accumulation of cytosolic Ca2+ in Alzheimer disease than in control lymphoblasts, which is better appreciated when the Ca2+ efflux is inhibited. Thus, the authors concluded that Alzheimer disease lymphoblasts have a lower Ca2+ buffering capacity than normal cells, probably because of changes in availability or intrinsic functional properties of the intracellular Ca(2+)-binding structures. Aging alters the kinetics of the Ca2+ replenishment in lymphoblasts in a manner that resembles Alzheimer disease. However, unlike Alzheimer disease, aging does not change the maximum cytosolic-free [Ca2+], suggesting that the mechanisms underlying the altered Ca2+ homeostasis in aging and late-onset Alzheimer disease are different.