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.
Ibarreta
D
D
Department of Pathophysiology and Human Molecular Genetics, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain.
Parrilla
R
R
Ayuso
M S
MS
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism* / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D012016:Reference Values
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D002118:Calcium