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Introduction

Scientists have made many breakthrough discoveries about the way Alzheimer's disease begins and progresses. Researchers have made tremendous strides in understanding the major pathological characteristics of AD in the brain, beta-amyloid plaques and neurofibrillary tangles, though our knowledge is still incomplete. The work being done now revolves around attaining a more thorough picture of how all the events involved in the Alzheimer's disease process fit together, and how the complex processes at work in AD have ripple effects throughout the brain, from neuronal overexcitation and inflammation to synaptic dysfunction and hippocampal hyperactivation. All this research into basic science is important because it opens up a variety of possibilities for treatment and prevention.

Each time a scientist clarifies a new aspect of the disease process, he or she may have found another chance to modify or change that process. For example, once researchers identified the two enzymes that cleave the APP protein to form beta-amyloid peptides (that can clump together to form plaques in the brain), drugs to block those enzymes were developed, and now some are being tested in clinical trials. Many more drugs in clinical trials have come out of basic science findings that illuminate various steps along the disease process. As we uncover more about the disease process, even more drug targets are certain to be identified.

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  Examining brain tissue taken on autopsy

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  Sister Alice Caulfield

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  Dr. Carl Cotman

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  Transgenic mouse used in AD research study

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  Dr. Craft comparing high-fat to low-fat diet

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  A Sun City resident hits the gym

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  Water maze tests the ability of the mouse to remember

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  Dr. Paul Aisen

Another major advance has been the emerging consensus that the processes that culminate in AD are set in motion long before symptoms appear, and that the ability to identify people at a pre-symptomatic stage increases the chance of having a positive drug effect before cognitive decline becomes life-changing. The ability to define mild cognitive impairment (MCI) as an early stage in functional decline represents another step forward in accurately delineating the boundaries between normal and impaired cognition that can progress to AD. Improved tools for early diagnosis will help scientists test drugs on the right populations, ideally early in the disease process before symptoms begin.

Both basic science and drug development have benefited from the groundbreaking advances in imaging technologies that have occurred in the last few years. Imaging tools currently used in research have allowed scientists to see the pathologies of AD in living brains, shedding new light on many aspects of the disease process. Imaging is now also a key element of many clinical trials, making it possible to start correlating physical changes in the brain with alterations in thinking and memory abilities.

Scientists are singling out and studying many possible contributing causes of AD, including risk factors such as vascular disease, diabetes and insulin resistance, and inflammation, all of which in turn can be influenced by inherited susceptibility genes. While we cannot do anything about our individual genome and age, research is suggesting that some lifestyle factors that are within our control may be important. There is accumulating evidence to suggest that exercise, diet, and cognitive stimulation may make a difference to the aging brain, particularly when maintained over the course of a lifetime. Scientists have also begun to explore the therapeutic implications of studies that have associated AD with vascular disease and diabetes.

Many people wonder why it is taking so long to develop drugs that can help their loved ones or decrease their own risk. Their impatience is perfectly understandable. But AD is a complicated disease, and the process by which a safe, effective drug can be brought to market is a difficult one to traverse. Developing a new drug takes a lot of time, money, scientists trained in many different disciplines, and research volunteers—not to mention scientific brilliance and a lot of luck. Fortunately, in the world of AD drug development, many scientists and organizations are working very hard to develop drugs that will make a difference.

The search for drug treatments begins with basic science and may well end with a new outcome for millions of people. We can chart a new path toward the future for AD research by supporting continued basic scientific inquiry and the advances in drug development and therapeutic strategies that will come from it. In the final chapters of this book, we step inside the laboratories and learn about the clinical trials that are bringing that future ever closer.

In a little more than twenty years, the science has come to a point where the expectation is now that a treatment will definitely be found to slow or even prevent the disease. "Our only sorrow," Dr. Steven DeKosky said, "is that we can't do it instantly."

Next: Building Cognitive Reserve

Excerpted from THE ALZHEIMER'S PROJECT: MOMENTUM IN SCIENCE, published by Public Affairs, www.publicaffairsbooks.com.