Korean Journal of Biological Psychiatry

Lowered immune function in the senile dementia patients may be related to the abnormal metabolism of amyloid precursor protein(APP). To investigate the possibility of an abnormal metabolism of APP in lymphocytes and the possible role of APP in the activation of lymphocytes in senile dementia patients, immunohistochemical study of rat spleen and fluorescence activated cell sorter analysis(FACS) of human lymphocytes with the specific antigen for each lymphocyte and double fluorescent marker with antibody to APP were performed. After stimulating lymphocyte with phytohemagglutinin(PHA), APP mRNA and protein were extracted and quantified and the influence of β-amylodi protein(Aβ) specific antibody on lymphocyte division was investigated. In spleen, the majority of cells showing Aβ immunoreactivity was found in the T-cell dependent zone. FACS indicated that around 90% CD₄(+) T-cells and 60% of CD₈(+) T-cells were immunoreactive to Aβ specific antibody(mAb 4G8). Northern blot analysis shows that lymphocyte APP mRNA was gradually increased to reach a maximum at 3 days after activation with lectin mitogen PHA. However, the Aβ immunoreactivity on cell surface remained constant during stimulation with PHA, indicating that the release of APP(secreted from of APP) might be increased. A very large increase in soluble APP secretion was observed in T-lymphocyte upon activation, but only low levels in the resting state. Immunoblot was carried out on the protein obtained from cell lysate after stimulating lymphocyte by applying PHA to the cultured lymphocyte, and the result was that Aβ band of immature form under 116 KDa marker decreased as the duration of culture was increased after PHA stimulation. The monoclonal Aβ specific(4G8) and polyclonal APP antibodies did not inhibit the [³H]-thymidine uptake of mitogen-treated lymphocytes significantly, suggesting that mitogenesis can not be inhibited by specific Aβ and polyclonal APP antibody. These results suggest that APP is expressed in T cell and might be closely associated with the function of T cells.

Keywords Dementia of the alzheimer type;Immune function;Gene expression;Amyloid precursor protein.