Engineered Pathology Models

Although aged dogs and primates provide some insight into spontaneous AD and can be invaluable in testing the safety and efficacy of diagnostic and therapeutic agents, they are long-lived and do not reproduce all of the pathological features of the human disease. Engineered models attempt to combine knowledge gained from the familial forms of AD with transgenic technology to individually reconstruct the major components of the pathology. In order for such an approach to completely succeed, either the prime mover in the disease process has to be addressed or the complex pathology has to be an approximately linear combination of two or more pathologies, such as plaques and tangles. In the case of overlapping pathologies, each transgene should be able to induce key characteristics of AD pathology. Finally, the organism must be capable of reflecting the impact of the pathology in a recognizable way, preferably with behavioral signs and symptoms similar to those in humans with AD.

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