Intracellular calcium response is reduced in CD4+ lymphocytes in Alzheimer's disease and in older persons with Down's syndrome.
Abnormalities in intracellular free calcium ([Ca2+]i) regulation are likely to play a role in brain aging and have been described in cells from patients with Alzheimer's disease (AD). [Ca2+]i acts as a second messenger in transmembrane signaling and regulates diverse functions in many cell types. Therefore, abnormalities in [Ca2+]i response may have far-ranging effects. Using flow cytometric assay for [Ca2+]i, we examined whether mitogen-induced increases in [Ca2+]i are abnormal in CD4+ T-lymphocytes from patients with familial AD (FAD), other AD, and Down's syndrome (DS) compared to age-matched controls. We observed that the peak [Ca2+]i responses were significantly decreased in CD4+ cells from 6 FAD patients (59% of control), 34 other AD patients (69% of age-matched control), and 6 older persons with DS (> 25 years old, 47% of control), after stimulation with 10 micrograms/ml anti-CD3 monoclonal antibody (mAb). The number of CD3 receptors on T lymphocytes of the AD patients was not decreased. In contrast, lymphocytes from subjects with FAD, other AD and older DS patients had no decrease in response to phytohemagglutinin (30 micrograms/ml). CD3 and related classes of membrane receptors are present on many cells of the central nervous system. Therefore, receptor signaling defects via this receptor in T lymphocytes of AD patients may be relevant to the central nervous system pathology seen in AD and DS.
Grossmann
A
A
Department of Pathology, University of Washington, Seattle 98195.
Kukull
W A
WA
Jinneman
J C
JC
Bird
T D
TD
Villacres
E C
EC
Larson
E B
EB
Rabinovitch
P S
PS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004314:Down Syndrome / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D007211:Indoles; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015704:CD4 Antigens; D005456:Fluorescent Dyes; D007211:Indoles; C048960:indo-1; D002118:Calcium