Effects of beta-amyloid Peptide on the Proliferation and Cytokine Production of Mononuclear Cells from Patients with Dementia of the Alzheimer's Type

Chae, Jeong Ho; Paik, In Ho

Abstract

OBJECTIVES: Deposition of the beta-amyloid(Abeta) peptide in the senile plaque has been thought as a major etiologic factor for the development of Alzheimer's disease. Among the hypotheses suggested to explain the mechanism by which Abeta causes Alzheimer's disease, the immune processes have been considered as crucial events in the pathophysiology of the Alzheimer's disease. This study examined the effects of Abeta on the proliferation and the production of IL-1beta(interleukin-1beta) and TNF-alpha(tumor necrosis factor-alpha) in peripheral blood mononuclear cells isolated from the patients with Alzheimer's disease, vascular dementia, and normal elderly control subjects.
METHODS
Nineteen patients with Alzheimer's disease, 22 patients with vascular dementia, and 19 controls were participated in this study. Peripheral blood mononuclear cells were obtained from each donors, and subjected to the proliferation assays in response to the stimulation of phytohemagglutinin-P(PHA-P) and Abeta. The levels of IL-1beta and TNF-alpha from the culture supernatants of the cells before and after the stimulation of Abeta were also determined by enzyme linked immunosorbent assay.
RESULTS
The results were as follows: 1) The proliferation of mononuclear cells in response to PHA-P were not different among three groups. 2) When compared to PHA-P, the proliferation responses of mononuclear cells to Abeta were insignificant in all experimental groups. However Alzheimer's disease group showed greater stimulation index than vascular dementia and controls. 3) IL-1beta production was higher in the vascular dementia group than Alzheimer's disease and control groups both before and after the stimulation of Abeta. However the stimulation ratio of before and after Abeta stimulation was highest in Alzheimer's disease group. 4) TNF-alpha production was higher in Alzheimer's disease group than controls both before and after the stimulation of Abeta.
CONCLUSION
These findings suggest that the immune responses to the stimulation of Abeta may be enhanced in patients with Alzheimer's disease compared to vascular dementia and control groups, supporting the immune hypothesis for the pathophysiology of Alzheimer's disease.