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 pre viously shown that patients with AIDS dementia had an elevated percentage o f a CD14(+)/CD69(+) subset and that conditioned media from these M/M phi cu ltures were toxic to neural cultures. We therefore postulated that patients with AD might likewise have a higher monocyte subset and that this would b e 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 scatt er (SSC), a measure of cellular granularity was also elevated in AD patient s (p = 0.02). The elevated expression of human leukocyte antigen (HLA-DR) w as 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 fur neurotoxicity three of the five culture supernatants fr om AD patients induced apoptosis in neural cell aggregate cultures. Electro phoretic mobility shift assays revealed that. these three supernatants also triggered NF-kappa B translocation to the nucleus. Surprisingly, in vitro a neurotoxicity was induced by M/M phi supernatants having a lower percenta ge 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 bur may nor be directly inv olved in neural cell toxicity.