Th1 responses to beta-amyloid in young humans convert to regulatory IL-10 responses in Down syndrome and Alzheimer's disease

Aβ1–42-specific antibodies and T-cell proliferation point to the existence of a memory response to Aβ1–42 in humans. Using ELISPOT, we studied Aβ1–42-specific T cells in individuals of various ages, and in subjects with Trisomy 21 or Alzheimer's disease. We show for the first time that Aβ1–42-specific Th1-type T-cell memory is present in young humans, producing high levels of IFN-γ and IL-2. With increasing age, the production of IFN-γ and IL-2 decreases but is not discontinued in healthy subjects and is accompanied by a sharp rise in CD4+ T-cell-derived regulatory IL-10 production. In contrast, individuals with Trisomy 21 and with Alzheimer's disease produce IL-10 only in the absence of any effector cytokine. This signifies a switch from a Th1 effector to an IL-10 mediated regulatory response.