Loss of calcium-homeostatic mechanisms in polymorphonuclear leukocytes of demented and nondemented elderly subjects.
The calcium homeostatic mechanisms were explored in 31 aged individuals some of whom suffered from dementia (11 Alzheimer's disease, 5 other dementias, 15 cognitively normal individuals). Their mean age was 81.2 +/- 9.2 years, varying from 60 to 96 years. Polymorphonuclear leukocytes (PMNs) were isolated from freshly drawn citrated blood and loaded with Fura-2. Resting intracellular free calcium values, [Ca2+]o, were recorded as well as the calcium transients produced by formyl-methionyl-leucyl-phenylalanine 10(-8) M:delta [Ca2+]i. The return to prestimulation values was also recorded. Average [Ca2+]o was 64.6 +/- 16.0 nM and the average delta [Ca2+]i 77.6 +/- 52.7 nM. No correlation was found with age within the range explored nor was there any difference in calcium transients between demented and nondemented patients. The most surprising finding was the inability of about 30% of all examined patients' PMNs to return the elevated [Ca2+]i values to prestimulation values. For some patients, elevated [Ca2+]i remained at the higher value, for others [Ca2+]i continued to rise. Those who could down-regulate poststimulation values did it only very slowly. Previous results obtained with leukocytes from younger individuals (under 45 years) showed a rapid return to prestimulation values. It appears that this loss of calcium-homeostatic mechanisms in old individuals is a progressive process which involves a relatively high proportion of the investigated subjects. The rate of decrease of intracellular calcium (measured by the slope P) did not correlate with diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Ghuysen-Itard
A F
AF
Laboratoire de Biologie du Tissu Conjonctif, URA CNRS 1460, Faculté de Médecine, Créteil, France.
Robert
L
L
Gourlet
V
V
Berr
C
C
Jacob
M P
MP
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood; D002118:Calcium / Q000097:blood*; D003704:Dementia / Q000097:blood*; D005260:Female; D006706:Homeostasis; D006801:Humans; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*
D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium