Alzheimer’s disease is the sixth leading cause of death in the United States, and the only one that can’t be prevented or slowed. Unlike cancer and heart disease, we currently lack both the tools to easily diagnose Alzheimer’s and the medications to effectively treat it.
There are many reasons for this. In sharp contrast to other illnesses, and despite many efforts, huge expense and hundreds of clinical trials, no new treatments for Alzheimer's disease have been approved in the last 16 years. The emphasis has been on drugs targeting beta-amyloid proteins, which clump into plaques in the brains of people with Alzheimer’s. Unfortunately, these approaches have not yet yielded the results we hoped for.
So now it’s time to target novel pathways to tackle this incredibly complex disease.
One reason this has been such a challenge has been the absence of affordable and noninvasive biomarkers that can be easily deployed in doctors’ offices around the world. Biomarkers to specific molecular targets can be used to predict the likelihood a person will develop Alzheimer’s disease (such as the currently available blood tests for apolipoprotein E genotyping) and provide a diagnosis even before symptoms are noticeable (such as the currently available positron emission tomography [PET] amyloid scans and cerebral spinal fluid [CSF] tests). Biomarkers measure how the body responds to a treatment, as was done most recently by Biogen with its anti-beta amyloid vaccines. Ultimately, biomarkers can determine which therapies would be most effective for an individual.
While Alzheimer’s lacks these simple and inexpensive tests, many other diseases, including diabetes, hypertension, hyperlipidemia and cancer have such tools to advance treatment options and clinical care. In heart disease, measuring serum cholesterol levels has long been used as a biomarker to identify those patients at risk. The blood test is affordable and reimbursable. If cholesterol levels are high, drugs like statins can be prescribed to lower it. And lowering cholesterol reduces the risk for heart disease. Doctors can use cholesterol levels to see if a prescribed drug is working or needs an adjustment. Since blood cholesterol is also recognized as a surrogate biomarker by the FDA, clinical trials can simply show a drug lowers cholesterol and get approval.
Although diagnostic and prognostic biomarkers such as PET brain amyloid imaging and CSF based amyloid and tau tests are currently clinically available for Alzheimer’s disease, only 5 percent of patients in the U.S. have been tested with these confirmatory clinical biomarkers due to cost and access restrictions. And payers, including the Centers for Medicare & Medicaid Services (CMS), won’t cover these tests based on the perception that a definitive diagnosis has little clinical value.
However, recent studies on the value of PET amyloid brain scans, supported by CMS, have shown that “dementia expert” doctors practicing in the community misdiagnose Alzheimer’s disease in about 50 percent of cases and change their management and treatment of patients nearly 70 percent of the time when this test is used. An inexpensive blood test, covered by insurance, which can be performed in any clinical setting, would have a big impact on patients and their caregivers.
Recently, the FDA issued guidelines recognizing the important role of biomarkers in demonstrating efficacy (especially in early stage) clinical trials for Alzheimer’s disease. These new guidelines are a major step forward for developing drugs for Alzheimer’s.
We must now develop inexpensive and noninvasive biomarkers, preferably blood tests, that will help diagnose Alzheimer’s disease and track the effectiveness of treatments. This will help to make clinical trials more rigorous, affordable and efficient, and accelerate the development of new drugs and will improve clinical care by providing access to accurate diagnosis.
That is why the Alzheimer’s Drug Discovery Foundation (ADDF) is honored to partner with Bill Gates, the Dolby family, the Charles and Helen Schwab Foundation and others to create Diagnostics Accelerator, an initiative that advances the development of novel biomarkers from blood and other peripheral fluids and tissue to diagnose Alzheimer’s disease and related dementias. Using the biomarker specific model of precision medicine, we will be able to predict more accurately which treatment and prevention strategies will work in different at-risk populations of people who have Alzheimer's disease or other forms of dementia, as we can now do in cancer, heart disease and other chronic diseases of aging and old age.