Readers who followed Tom Fagan’s Keystone Symposium coverage of how a particular form of neuroinflammation appears to drive tauopathy while ameliorating amyloid pathology can now take in the full dataset. Tomorrow in Neuron, researchers from Bruce Lamb’s and Richard Ransohoff’s laboratories at the Cleveland Clinic Foundation in Cleveland, Ohio, report results of various experimental approaches suggesting that the fractalkine receptor CX3CR1 on microglial cells might be worth a look as a potential new therapeutic target. Led by first author Kiran Bhaskar, the scientists lay out how activated microglia cause worse tau hyperphosphorylation in mice missing this receptor than in mice that have it. Going beyond the Keystone presentation, the paper reports behavioral impairments in fractalkine receptor-deficient mice; it also implicates the interleukin-1 receptor and contains more mechanistic details on the underlying signaling cascade.
In the September 23 American Journal of Pathology, Sungho Lee and colleagues working with the same senior investigators published the amyloid half of the CX3CR1 story. Curiously, it cuts the opposite way, whereby amyloid pathology in an AD model is milder when the fractalkine receptor is absent in the mouse, probably because the microglia have a greater appetite for phagocytosing amyloid deposits. Together with another recent study on CX3CR1-deficient mice (Fuhrmann et al., 2010), this topic has stimulated scientific discussion about exactly what this receptor does to tau pathology, amyloid pathology, and the survival of embattled neurons. —Gabrielle Strobel