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). [Ca^2-]_iacts as a second messenger in transmembrane signaling and regulates diverse functions in many cell types. Therefore, abnormalities in [Ca²⁺]_iresponse 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⁺]_iresponses 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 μg/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 μg/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.