Why Has Research into Alzheimer's Disease Been So Hard?

Alzheimer’s disease is ruthless. For the 5.7 million Americans living with the condition, coping with the loss of cognitive functioning is a daily uphill battle. Currently, there are no effective treatments that modify the course of Alzheimer’s, and once diagnosed, the average life expectancy is seven years.

The history of research into treatments for Alzheimer’s is filled with setbacks. Between 1998 and 2017, 146 candidate medicines were unsuccessful in clinical trials for Alzheimer’s. In the same timeframe, just four received U.S. Food and Drug Administration approval. Moreover, these approved medicines treat only symptoms and are unable to slow the disease’s progression.

Why, when we have seen such progress in our ability to treat other diseases, such as cancer, diabetes and HIV, has progress in Alzheimer’s research been so difficult to achieve? Several factors make Alzheimer’s uniquely challenging to research and treat:

Alzheimer’s progresses over the course of years, not months, and patients can sometimes have the disease for 20 years before showing symptoms. By the time cognitive functioning is impaired, the disease is often so advanced that intervening treatments may not have much of an effect. Thus, it is extremely difficult to find clinical trial participants for medicines that can potentially treat Alzheimer’s in its earliest stages because patients are usually unaware they are in the early stages of the disease.

Alzheimer’s symptoms can mimic those of many other diseases, and the condition cannot be definitively diagnosed with any single lab test, scan or exam. Instead, doctors generally rely on evaluation of symptoms of the disease, and are increasingly using imaging tests, particularly in research. However, non-imaging biomarkers are needed to advance our capabilities to more easily monitor disease progression and response to treatment as well as improve the rigor and efficiency of clinical trials.

Currently, researchers understand that abnormal fragments of a protein called beta-amyloid accumulate to form “plaques” in the brain of individuals with Alzheimer’s, particularly in regions that support memory. In addition, the accumulation of tau proteins is another hallmark of the disease, but researchers are still debating whether these characteristics of Alzheimer’s are causes or symptoms of the disease.

Despite these challenges and the many setbacks we have seen in the pipeline, there is still reason to hope. Researchers learn from every unsuccessful medicine in the pipeline and use those findings to inform future research. Right now, biopharmaceutical companies are researching 92 potential medicines for the treatment of Alzheimer’s. An analysis by UsAgainstAlzheimer’s of medicines in development found that of those in Phases II and III, approximately 75 percent have the potential to be disease-modifying treatments.

Setbacks are an inherent part of the drug development process, particularly in the case of Alzheimer’s. But these setbacks don’t necessarily mean progress hasn’t been made. Despite the incredibly challenging hurdles, most Alzheimer’s researchers agree that with very failure comes a lesson, and eventually, these lessons will lead to the breakthrough we need.