Amyloid precursor protein expression in circulating monocytes and brain macrophages from patients with HIV-associated cognitive impairment

We examined amyloid precursor protein (APP) surface expression on circulating leukocytes and in brain tissues from normal individuals and HIV+ subjects with cognitive impairment. Most monocytes, and a subset of B-lymphocytes, expressed APP, while T-lymphocytes, granulocytes, and natural killer (NK) cells did not. CD14bright/CD16+ monocytes expressed the highest levels, and CD14dim/CD16+ cells were negative, suggesting a relationship with activation. Higher APP+ monocyte levels correlated with increased numbers of CD16+ monocytes, but not with the degree of cognitive impairment. Treatment of monocytes with M-CSF, but not LPS, upregulated APP expression. In the brain, APP appeared as axonal immunoreactivity and diffuse plaques, and APP+ perivascular macrophages were seen in cases with severe dementia. APP may facilitate monocyte entry into the brain.