Antibodies against amyloid-β, which accumulates in the brains of people with Alzheimer disease, can help clear inclusions of the protein from mice engineered to overexpress it. Robert Brendza et al. now show that such treatment also reduces some of the neuronal damage associated with the buildup of amyloid-β.

In Alzheimer patients and the engineered mice, dystrophic neurites—large, swollen axons and dendrites—form around extracellular plaques that contain amyloid-β. To visualize the plaques and associated neurites, the researchers imaged the mice using multiphoton microscopy. They used a fluorophore that binds amyloid-β (blue), and mice engineered to express yellow fluorescent protein (green) in neurons, lighting up the blebs and swellings characteristic of dystrophic neurites. The researchers then treated the mice with antibodies against amyloid-β and looked at their brains three days later. In the 20 January issue of the Journal of Clinical Investigation they report that the treatment reduced the number of dystrophic neurites by about 20 percent, and reduced their size. The data are consistent with the amyloid hypothesis, that the accumulation of amyloid-β in the brain drives Alzheimer disease.