The amplifying effect of beta-amyloid fragment 25-35 (beta A25-35) on the mitogen-induced rise of free intracellular calcium in circulating lymphocytes was strongly reduced in 24 patients with Alzheimer's disease when compared with elderly, non-demented controls. Low beta-amyloid responses were significantly correlated with the presence of the apolipoprotein E epsilon 4 allele, suggesting a dose effect.