Elevation of CD69+ monocyte/macrophages in patients with Alzheimer's disease.

In this report, we examined the presence of the activation marker, CD69, on monocytes derived from patients with Alzheimer's disease (AD). We have previously shown that patients with AIDS dementia had an elevated percentage of a CD14+/CD69+ subset and that conditioned media from these M/M phi cultures were toxic to neural cultures. We therefore postulated that patients with AD might likewise have a higher monocyte subset and that this would be associated with neural toxicity. Flow analysis showed that AD patients (n = 13) had a higher percentage of CD69+ M/M phi over age matched controls (n = 14); this trend was statistically significant (p = 0.006). Side scatter (SSC), a measure of cellular granularity was also elevated in AD patients (p = 0.02). The elevated expression of human leukocyte antigen (HLA-DR) was not found to be significant between age-matched controls and AD patients. When conditioned media from M/M phi from five AD and two control patients were evaluated for neurotoxicity, three of the five culture supernatants from AD patients induced apoptosis in neural cell aggregate cultures. Electrophoretic mobility shift assays revealed that these three supernatants also triggered NF-kappaB translocation to the nucleus. Surprisingly, in vitro neurotoxicity was induced by M/M phi supernatants having a lower percentage of CD14+/CD69+ cells. Elevation of the CD14+/CD69+ subset in AD patients may therefore represent a manifestation in the peripheral blood of the pathological events occurring in the brain but may not be directly involved in neural cell toxicity.