The helping and hurting hands of microglia

By monitoring the movement of microglia ― immune cells of the brain ― in a mouse model of Alzheimer's disease (AD), scientists report that neuronal loss in the disease model is mitigated if the microglia's abilities to recognize and move towards neurons are disrupted. These results, published online this week in Nature Neuroscience, could be important in finding new targets for the development of therapeutic strategies to combat neuron loss in AD.

Progressive neuronal loss is a hallmark of AD, though the exact role of immune response in the disease progression is unclear. For example, microglia can eliminate amyloid beta aggregation, a common protein build-up found in AD brains. However, microglia are also known to be neurotoxic in the rodent models of Parkinson's disease and amyotrophic lateral sclerosis (ALS). Little is known about neurotoxic functionality of microglia in AD.

In order to better understand if microglia is involved in AD-related neuronal death, Jochen Herms and colleagues used in vivo imaging to simultaneously visualized neurons and microglia in the brains of mice in a rodent model of Alzheimer's disease. By imaging these cells in the same live animals up to four weeks, the scientists found that microglia are locally recruited to neurons before, but not after, cells begin to die and be eliminated. However, when the same in vivo imaging was conducted on mice lacking Cx3cr1 ― a gene for a microglial receptor crucial in neuron-microglia communication ― neuron loss in the mouse model of AD was prevented. These findings also suggest that microglia can be either beneficial or detrimental to neuronal death that is context-dependent on the type of neurodegeneration.