Alzheimer's disease is the sixth leading cause of death in the U.S., and unlike with cancer and heart disease, we lack the tools to effectively diagnose and treat it. In sharp contrast to other illnesses and despite many efforts, huge expense and hundreds of clinical trials, no new treatments have been approved in the past 16 years. The emphasis has been on drugs targeting beta-amyloid proteins, which clump into plaques in the brains of afflicted people. Unfortunately, these approaches have not yet yielded the results we hoped for.
So now it is time to target novel pathways to tackle this incredibly complex disease. This has been a challenge because of the absence of affordable and noninvasive tests based on biomarkers that doctors can easily use in their offices. The alternatives have been expensive and invasive spinal taps or neuroimaging tests that can be performed only in a hospital or freestanding radiology office. New biomarkers are needed for specific molecular targets that can be used to subtype patients; for predicting the likelihood that they will acquire Alzheimer's; and possibly for providing a diagnosis even before symptoms are noticeable, enabling prevention. That is, they could do what currently available amyloid positron-emission tomography (PET) scans and cerebrospinal fluid tests do. Biomarkers can also be used to enroll patients in clinical trials directed to a specific target, such as beta-amyloid, and to measure how the body responds to a treatment—as was done most recently by Biogen with its anti-beta-amyloid monoclonal antibody. Ultimately biomarkers can determine which therapies would be most effective for an individual.
Such tools are already available for other diseases, including diabetes, hypertension, hyperlipidemia and cancer. In heart disease, for instance, serum cholesterol levels, which are measured after simply drawing blood with a needle stick, have long been used as a biomarker to identify patients at risk. The test is affordable and generally covered by employers or health insurance providers, including Medicare. If blood levels are high, drugs such as statins can be prescribed to lower cholesterol and with it the risk for heart disease. Doctors can also use cholesterol levels to see if a prescribed drug is working or needs an adjustment. LDL cholesterol is also recognized as a biomarker for heart disease risk by the Food and Drug Administration, so clinical trials can show that a drug lowers cholesterol and get approval for it.
Despite the existing tests for diagnostic and prognostic biomarkers, few patients in the U.S. have been tested with these confirmatory tests because of cost and access restrictions. And payers, including Medicare, will not cover amyloid PET scans, based on the perception that a definitive diagnosis has little clinical value.
But recent studies on the value of PET beta-amyloid brain scans, supported by the Centers for Medicare & Medicaid Services, have shown that practicing “dementia expert” doctors misdiagnose Alzheimer's 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 in clinical trials for Alzheimer's (especially early-stage ones). These new guidelines are a major step forward for fast-tracking drugs for the disease.
We need comparable tests—preferably blood tests—to help diagnose Alzheimer's and evaluate treatments. This will aid us in making clinical trials more rigorous, affordable and efficient, will accelerate drug development and will improve clinical care by providing access to accurate diagnoses. A new initiative called the Diagnostics Accelerator, under the auspices of the Alzheimer's Drug Discovery Foundation, aims to develop novel biomarkers from blood and accessible fluids and tissue. Such markers, specifically tied to Alzheimer's or other forms of dementia, will allow us to predict more accurately which treatment and prevention strategies will work in at-risk populations, as we can now do in cancer, heart disease and other diseases of aging.