Insights into Abeta and presenilin from a canine model of human brain aging.

In this review, we describe insights into beta-amyloid (Abeta) production using aged dogs as a model of human brain aging. The advantage of using dogs is that they naturally accumulate Abeta neuropathology with age. In parallel, dogs also develop age-associated learning and memory impairments. Thus, dogs can complement existing transgenic and nonhuman primate models typically used in aging studies. Dogs can live up to 18-19 years of age and companion dogs share the same environment as humans. Morphological brain changes as a function of age are clearly visible in vivo using magnetic image resonance scans. At the light microscopic level, dogs accumulate diffuse plaques with a distribution similar to that observed in human brain. Confocal studies suggest that Abeta accumulates on neuronal membranes in a segregated pattern. This pattern has been confirmed at the ultrastructural level using electron microscopy and provides insight into the deposition of Abeta into the extracellular space, possibly prior to overt plaque formation. Further, double immunogold labeling studies demonstrate that Abeta associated with the plasma membrane is colocalized with presenilin. These in vivo observations suggest a common site for both Abeta and presenilin supporting the hypothesis that the latter is involved with APP processing.