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.
Vehmas
Ari
A
Department of Neurology, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287, USA.
Lieu
James
J
Pardo
Carlos A
CA
McArthur
Justin C
JC
Gartner
Suzanne
S
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001921:Brain / Q000166:cytology*; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods; D015658:HIV Infections / Q000150:complications / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D017452:Receptors, IgG; D016173:Macrophage Colony-Stimulating Factor