Credit: ©Lisa F. Young

Alzheimer's disease is one of the most feared—and most prevalent—afflictions of the elderly, affecting as many as half of the population over 85 years old. Much of the fear of this disease stems from its bleak prognosis and inadequate treatment, both symptoms of our cursory understanding of the disease. Now, a new study on a mouse model of Alzheimer's sheds light on the progression of this haunting affliction that may help arrest its development.

In the study, led by Andrew Luster at Harvard Medical School (Boston, MA), researchers crossed two kinds of transgenic mice. The first type of mouse, an established murine model of Alzheimer's disease, expresses human amyloid precursor protein (APP), which is transformed in the brain into β-amyloid, deposits of which are the hallmark of Alzheimer's. The second type of mouse is deficient in CCR2 (CCR2−/−), a receptor involved in chemotaxis that is expressed by microglia and monocytes, two kinds of immune cells that can be found in the brain.

Luster and his team crossbred these two types of mice, producing offspring that express human APP but lack CCR2 (APP-CCR2−/−). They found that these mice accumulated significantly more β-amyloid in their brains and had starkly higher mortality as compared to mice expressing human APP alone (Nat. Med., April). Moreover, the study also showed that the APP-CCR2−/− mice had 80% fewer microglia and monocytes in their brains, suggesting that the increased accumulation of β-amyloid—and resulting mortality—is related to the absence of these immune cells.

Presumably, the missing CCR2 is responsible for directing the microglia and monocytes to migrate from the blood and other areas to sites of β-amyloid deposits in the brain. This conclusion squares with another finding that CCL2, the main chemoattractive ligand for CCR2, is increased in humans with Alzheimer's disease. But even if this hypothesis is correct, much still remains unsolved. For instance, if microglia and monocytes are indeed involved in clearing β-amyloid deposits from the brain, is malfunctioning CCR2, at least in part, responsible for Alzheimer's? Or, can clinical intervention aid monocytes and microglia to reverse (or at least slow down) the memory loss and other symptoms associated with Alzheimer's? Hopefully, continued investigation of CCR2 will yield life-altering answers to these and other questions about this vexing disease.