Neurocytopathic Effects of β -Amyloid-Stimulated Monocytes: A Potential Mechanism for Central Nervous System Damage in Alzheimer Disease

• Published in: Proceedings of the National Academy of Sciences - PNAS 1996-04, Vol.93 (9), p.4147-4152
• Main Authors: London, Jill A., Biegel, Diane, Pachter, Joel S.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - pharmacology; Animals; Animals, Newborn; Brain; Cattle; Cell Aggregation - drug effects; Cell Death; Cell Survival; Cells, Cultured; Central nervous system; Cerebral Cortex - pathology; Coculture Techniques; Cultured cells; Humans; Macrophages; Macrophages - cytology; Macrophages - drug effects; Macrophages - physiology; Microglia; Microscopy, Confocal; Monocytes; Monocytes - cytology; Monocytes - drug effects; Monocytes - physiology; Nerve tissue; Neurology; Neurons; Neurons - pathology; Neurotoxins; Organ Culture Techniques; Peptides; Rats; Serum Albumin, Bovine - pharmacology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.9.4147

Growing evidence indicates that cells of the mononuclear phagocyte lineage, which includes peripheral blood monocytes (PBM) and tissue macrophages, participate in a variety of neurodestructive events and may play a pivotal role in neurodegenerative conditions such as Alzheimer disease. The present study sought to determine whether exposure of PBM to β -amyloid peptide (Aβ ), the major protein of the amyloid fibrils that accumulate in the brain in Alzheimer disease, could induce cytopathic activity in these cells upon their subsequent incubation with neural tissue. PBM were incubated with Aβ for 3 days, centrifuged and washed to remove traces of cell-free Aβ , and then applied to organotypic cultures of rat brain for varying periods of time. By using a cell-viability assay to quantitate neurocytopathic effect, an increase in the ratio of dead to live cells was detected in cultures containing Aβ -stimulated PBM versus control PBM (stimulated with either bovine serum albumin or reverse Aβ paptide) as early as 3 days after coculture. The ratio of dead to live cells increased further by 10 days of coculture. By 30 days of coculture, the dead to live cell ratio remained elevated, and the intensity of neurocytopathic effect was such that large areas of brain mass dissociated from the cultures. These results indicate that stimulation of PBM with Aβ significantly heightens their neurocytopathic activity and highlight the possibility that inflammatory reactions in the brain play a role in the neurodegeneration that accompanies Alzheimer disease.