Adapted from a summary by Dr. Joseph El Khoury
The brain’s immune system has been implicated as factor contributing to the development of Alzheimer’s disease for more that 20 years. Microglia, the main immune cells of the brain are recruited into the brain from the bone marrow and accumulate at an accelerated rate in Alzheimer’s disease. However, the exact role of the immune system in this disease has not been resolved. Based on test tube experiments, it was believed that microglia, the main immune cells of the brain, may protect brain cells by engulfing and digesting amyloid-beta, a toxic protein deposited in the brain of Alzheimer’s patients.
Other test tube data also suggested that amyloid-beta can activate microglia to secrete nerve toxins and may therefore cause nerve cell degeneration. To resolve this question, we used a mouse model of Alzheimer’s disease, and abolished trafficking of microglia into the brains of these mice by targeted deletion of the Ccr2 gene, which is involved in recruitment and accumulation of immune cells in inflammation. We found that Ccr2 deficiency and the resulting defect in microglial trafficking and accumulation, markedly accelerated early Alzheimer’s disease progression in these mice.
Ccr2 deficient Alzheimer’s mice accumulated amyloid-beta earlier around their blood vessels, and died prematurely, indicating that absence of early microglial accumulation leads to decreased amyloid-beta clearance and increased mortality. Therefore, our findings provide evidence in a living animal that the brain’s immune system plays a protective role in early Alzheimer’s disease by mediating the clearance of amyloid-beta. These findings are published in the March 11, 2007 edition of the journal Nature Medicine.
Alzheimer’s Disease Research, a program of the American Health Assistance Foundation, is proud to have funded Dr. Joseph El Khoury for this very important work.