The 2005-2006 AD Progress Report: A Journey’s Tale

Sometimes journeys are straightforward. Point B lies in a direct line some distance ahead of Point A. Other journeys are more circuitous—travelers must take many winding and intersecting paths, and even go around a few traffic circles to get from Point A to Point B. Scientific research in complex diseases like AD certainly falls into this latter category. Progress depends on the accumulation of results from many studies. Findings from one study add to or support findings from other studies. Unexpected findings can mean that investigators must head in a new direction. A promising track may suddenly become a scientific dead end, requiring researchers to rethink their original hypotheses. A possible intervention may have serious negative side effects in animals or humans, necessitating an alternative approach. Investigators may travel from laboratory "bench" to clinical "bedside" and back again before an intervention is thoroughly tested and refined.

By following many pathways over the past 30 years, scientists have built a solid body of evidence about AD. Initially, research defined the major characteristics of AD, the course of the disease, and some aspects of its etiology (causal factors). As this knowledge base developed, scientists were able to design increasingly sophisticated studies to understand more about the early changes in the brain of a person with AD, and the many factors that contribute to the development of these pathologies, or damage caused by the disease. They also were able to expand into other areas of research. These research paths necessarily intersect and depend on each other:

Test tube and animal studies are revealing fundamental information about why, how, and when biological events occur in AD. They provide a major foundation for translational research (research that facilitates the two-way transfer of knowledge between basic scientific observations and clinical care and clinical trials; see "How Do We Translate Scientific Discoveries Into Effective Treatments?" for more information). These studies also have increased our appreciation of the differences between species and the fact that findings in animals do not necessarily translate to humans.

• Epidemiologic studies in humans can show associations between basic characteristics and factors that are hypothesized to cause a disease. Epidemiologic studies are valuable because they pave the way for additional testing in clinical trials.
• Clinical trials test possible interventions suggested by test tube, animal, and epidemiologic studies. These trials can control variables known to be important, thereby lending greater certainty to conclusions about cause and effect (see "A Closer Look at Two Aspects of AD Clinical Trials" for more information).
• Findings from clinical trials feed back to suggest new pathways to explore in test tube, animal, and epidemiologic studies.

Part 2 of the 2005-2006 Alzheimer's Disease Progress Report describes recent milestones in this ongoing journey down the many paths of AD research.

In addition to a map, journeys also require a means of transport. Part 3 describes NIH programs and initiatives that have nurtured the essential research infrastructure, allowing scientists to push forward the basic science, conduct essential observational and clinical studies, and begin to develop new drugs and other treatment approaches.

Finally, travelers must plan ahead for future challenges as the journey unfolds. The final section of this report, Part 4, provides such an outlook for the future in AD research.

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