Changes of intracellular calcium regulation in Alzheimer's disease and vascular dementia.
Free intracellular calcium ([Ca2+]i) represents probably the most important intracellular messenger for many signal transduction pathways. Due to this crucial role of [Ca2+]i, it has been assumed that alterations of [Ca2+]i are critically involved in brain aging and in the pathophysiology of Alzheimer's disease (AD). This hypothesis is corroborated by several studies demonstrating changes of [Ca2+]i in peripheral cells from AD patients. However, the findings are still controversial. Using blood lymphocytes and neutrophils as two different peripheral model systems, we evaluated several parameters of intracellular Ca2+ regulation in a very large group of AD patients and non-demented controls. We found no major difference in Ca2+ homeostasis, since neither the basal [Ca2+]i, nor the activation-induced Ca2+ responses differed among neutrophils or lymphocytes from aged controls and AD patients. However, we observed a delayed Ca2+ response of AD lymphocytes after phytohemagglutinin (PHA) stimulation indicating an impaired function of Ca2+ influx-controlling mechanisms. Furthermore, we studied whether differences exist in Ca2+ regulation between lymphocytes from patients with vascular dementia and AD patients, to define AD-specific alterations and to distinguish between the two dementia groups and non-demented control subjects respectively. First evidences indicate that Ca2+ mobilization in lymphocytes is specifically impaired in lymphocytes from patients with vascular dementia.
Eckert
A
A
Department of Psychopharmacology, Klinikum Mannheim, University of Heidelberg, Federal Republic of Germany.
Förstl
H
H
Zerfass
R
R
Oster
M
M
Hennerici
M
M
Müller
W E
WE
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D002118:Calcium / Q000097:blood*; D015140:Dementia, Vascular / Q000097:blood*; D005260:Female; D006706:Homeostasis; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008137:Longitudinal Studies; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D012016:Reference Values
D002118:Calcium