The team examined 49 mice with a mutation in the gene for amyloid precursor protein (APP) similar to the genetic abnormality found in some families with a strong history of Alzheimers disease. All the mice developed plaques within a year, though to varying degrees. The researchers took advantage of these differences to investigate potential factors that predict the extent of plaque formation.
First, they measured baseline levels of two types of Ab in the animals blood, Ab40 and Ab42. The mice then were injected with m266 an antibody that the team previously discovered draws Ab out of the brain and into the surrounding blood without harming the animals and were periodically retested for blood Ab. After 24 hours, the researchers examined each animals brain tissue for plaques, focusing on two key regions involved in Alzheimers disease: the hippocampus and the cingulate cortex.
Before m266 injection, the amount of Ab in the animals blood did not correlate to the number of plaques in their brains. But within five minutes of m266 injection, Ab levels increased dramatically and did correlate with the amount of brain amyloid. This suggests that blood Ab levels do not reflect the progression of the disease unless the animal has been given m266.
According to DeMattos, blood Ab levels in humans also do not reflect the amount of amyloid plaques in the brain. The truly novel finding of our experiment is that a simple injection of m266 altered the metabolism of Ab and unmasked important correlations with brain pathology. Hopefully, we also will be able to alter the metabolism of Ab in humans.
The team used their data to develop potential models for estimating amyloid levels in the brain. Several factors, including overall levels of Ab after m266 injection and Ab40 levels 24 hours after injection, accurately revealed the extent of amyloid deposi
Contact: Gila Z. Reckess
Washington University School of Medicine