β-Amyloid precursor protein is detectable on monocytes and is increased in Alzheimer’s disease

Using the anti-beta-amyloid precursor protein (βAPP) monoclonal antibodies 4G8, 6E10 and 22C11 and flow cytometry, we report that human circulating peripheral blood monocytes display surface immunoreactivity for βAPP. In contrast, circulating lymphocytes do not possess cell surface βAPP immunoreactivity, despite similar levels of βAPP expression. Immunoblotting analysis showed that monocytes, but not lymphocytes, possess an 82kDa C-terminal βAPP fragment consistent with a processed transmembrane species. Monocyte surface βAPP was upregulated not, vert, similarthreefold by activation with lipopolysaccharide and interferon-γ; activation did not produce detectable βAPP on the cell surface of lymphocytes. Surface βAPP immunoreactivity was reduced in a normal aged population compared to normal young controls (Young = 81.07 ± 13.67 mean fluorescence units, Aged = 36.74 ± 3.81, p < 0.01), but was significantly increased in AD subjects compared to age-matched healthy controls (AD = 60.31 ± 7.42, p < 0.05). Our data suggest that a proportion of peripheral Aβ may be derived from monocyte/macrophages, and that defects in brain cell processing of βAPP in AD may be shared by this readily accessible peripheral cell.