During an annual check-up, the patient says: “Doctor, I saw a commercial about a blood test that can determine whether I will develop Alzheimer’s disease. I saw my mother go through it. I want to get tested.”
He refers to the new Blood-based biomarkers of Alzheimer’s. Despite showing no symptoms of Alzheimer’s disease – he manages his own finances, drives, shops and cooks elaborate meals for his wife – he is clearly worried.
The doctor responds, “Okay, there may be some out-of-pocket costs, but I can order the test.” He looks relieved. “But just to be sure,” she tells him, “we still don’t know what to do with a positive result.”
A new era of dementia care has been ushered in by the development of anti-amyloid antibodies for the treatment of Alzheimer’s disease. These therapies are the first FDA-approved treatments for AD in nearly 20 years. As a result of these disease-modifying treatments, the accurate and efficient detection of Alzheimer’s disease has become critical, especially as earlier detection allows for more effective treatment. With the advent of blood-based biomarkers, the ability to potentially detect Alzheimer’s disease before symptoms appear has brought new clinical and ethical challenges to the diagnosis and management of the disease.
Currently, the typical process of diagnosing Alzheimer’s disease can be difficult and often requires neuropsychological tests, MRIs, PET scans and CSF tests – all of which are expensive and only available in certain specialist clinics.
Enter the blood-based biomarkers that can detect the amyloid plaques and tau tangles that define Alzheimer’s disease through a simple blood test. These groundbreaking tests have a high diagnostic accuracy – approximately 85-90% – and, when combined with traditional tests, can effectively diagnose Alzheimer’s disease in patients with cognitive decline. It cannot be overstated how paradigm-shifting these two developments are for the diagnosis and treatment of Alzheimer’s disease. Since the approval of lecanemab in July 2023, we have achieved the ability to effectively detect and treat the underlying pathological process of Alzheimer’s disease, even though its full efficacy remains uncertain.
Back to our patient. Let’s say his blood test is positive for amyloid plaques and tau tangles. What now? He has no symptoms of Alzheimer’s disease and is fully functional for his age. You decide to refer him to a neurologist for further examination. They get an MRI, which shows that the brain is healthy. Neuropsychological examination is normal. At this point we are stuck – should we formally diagnose him as having Alzheimer’s, despite it turning out to be so no symptoms of the disease? And if so, should we start therapy with an anti-amyloid drug? Billions of dollars and the lives of millions of individuals depend on the answers to these questions.
The above scenario is illustrative of the complex challenges that blood-based biomarkers bring to the healthcare system. On the positive side, early detection allows individuals to make lifestyle changes to reduce the progression of Alzheimer’s disease. Increasing physical activity, improving diet and aggressively managing chronic conditions such as high blood pressure and diabetes have been linked less amyloid burden in the brain. For people with a family history of Alzheimer’s disease, testing blood-based biomarkers can provide crucial insights, allowing proactive steps to be taken even before symptoms arise. Finally, the anti-amyloid drugs, although not yet approved for asymptomatic patients, may offer the opportunity to slowing down disease progression if given early.
However, the promise is far from being realized. The clinical utility of these tests in asymptomatic individuals remains underexplored intense debateespecially since the presence of amyloid does not guarantee the development of Alzheimer’s disease. Meanwhile, a positive outcome can lead to significant problems if there is no clear path forward.
The financial implications of the widespread use of blood-based biomarkers are significant. These tests and subsequent treatments are expensive and may not be fully covered by insurance, placing a heavy financial burden on patients. This raises ethical questions about equity and access: who should be tested and who will bear the costs? Universal testing may lead to earlier interventions and better outcomes for some, but also increases the risk of overdiagnosis and overtreatment. In turn, widespread adoption of these tests could strain healthcare resources, potentially diverting attention from other critical areas.
It is therefore crucial that we develop strict standards in this area WHO should be tested and when. A research infrastructure should be established that aims to determine whether asymptomatic individuals with positive blood tests ultimately develop clinical Alzheimer’s disease and whether anti-amyloid therapies given to asymptomatic individuals prevent cognitive decline. The results of these studies should then be evaluated by an impartial organization, such as the US Preventive Services Taskforce, to establish guidelines for the use of blood-based biomarkers for screening in asymptomatic individuals. In the meantime, primary care providers, geriatricians, and neurologists should be ready to educate their patients about their potential benefits and limitations.
As we enter this new era of diagnostics and therapies for Alzheimer’s disease, we must be careful to balance the power of these tools with their risks and the costs they entail. The real-world implementation of blood-based biomarkers will require close collaboration between manufacturers, professional organizations, patient advocacy groups, and government agencies to ensure they are provided in an economical and equitable manner. Only through a careful and methodical approach to their integration into the healthcare ecosystem will the full potential of these technologies be realized.
Naveen Reddy is a health policy researcher and neurologist at the University of California, San Francisco. Kristine Yaffe is vice chair of psychiatry, neurology and epidemiology at UCSF and director of the Center for Population Brain Health at UCSF.