During an annual checkup, the patient says: “Doc, I saw a commercial about a blood test that can tell if I’ll develop Alzheimer’s. I watched my mother go through it. I want to get tested.”
He’s referring to the new Alzheimer’s blood-based biomarkers. Despite not showing any symptoms of Alzheimer’s — he manages his own finances, drives, shops, and cooks elaborate meals for his wife — he’s clearly worried.
The doctor replies, “OK, there might be some out-of-pocket costs, but I can order the test.” He looks relieved. “But just so you know,” she tells him, “we’re still not sure what to do with a positive result.”
A new age 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 released in nearly 20 years. As a consequence of these disease-modifying treatments, the accurate and efficient detection of Alzheimer’s has become paramount, especially as earlier detection allows for more effective treatment. With the advent of blood-based biomarkers, the ability to possibly detect Alzheimer’s disease before symptoms emerge has introduced new clinical and ethical challenges to the diagnosis and management of the disease.
At the moment, the typical process of diagnosing Alzheimer’s can be difficult and often requires neuropsychological batteries, MRIs, PET scans, and CSF testing — all of which are costly and only available at certain specialized clinics.
Enter the blood-based biomarkers, which can detect the amyloid plaques and tau tangles that define Alzheimer’s through a simple blood test. These ground-breaking assays come with high diagnostic accuracy — around 85-90% — and when combined with traditional testing, can effectively diagnose Alzheimer’s in patients with cognitive decline. It cannot be overstated how paradigm-shifting these two developments are for the diagnosis and treatment of Alzheimer’s. Since the approval of lecanemab in July 2023, we have acquired 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 returns positive for amyloid plaques and tau tangles. What next? He doesn’t have any symptoms of Alzheimer’s and is completely functional for his age. You decide to refer him to a neurologist for further evaluation. They obtain an MRI, which shows a healthy brain. Neuropsychological testing is normal. At this point, we’re stuck — should we formally diagnose him with Alzheimer’s despite showing no symptoms of the disease? And if so, do we then initiate therapy with an anti-amyloid agent? Billions of dollars and the lives of millions of individuals hinge upon the answers to these questions.
The above scenario is illustrative of the complex challenges that blood-based biomarkers present to the health care system. On the positive side, early detection allows individuals to incorporate lifestyle changes to reduce the rate of progression of Alzheimer’s. Increasing physical activity, improving diet, and aggressively managing chronic conditions like hypertension and diabetes have been associated with less amyloid burden in the brain. For those with a family history of Alzheimer’s, blood-based biomarker testing can provide critical insights, enabling proactive steps to be taken even before symptoms arise. Lastly, while not yet approved for asymptomatic patients, the anti-amyloid drugs may offer the possibility of slowing disease progression if administered early.
However, the promise is as yet far from being realized. The clinical utility of these tests in asymptomatic individuals is still under intense debate, particularly because the presence of amyloid doesn’t guarantee the development of Alzheimer’s. Meanwhile, a positive result can lead to significant distress if there isn’t a clear path forward.
The financial implications of widespread blood-based biomarker use are substantial. 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 cost? Universal testing could lead to earlier interventions and better outcomes for some, but it also increases the risk of overdiagnosis and overtreatment. In turn, the widespread adoption of these tests could strain health care resources, potentially diverting attention from other critical areas.
It is crucial, then, that we develop strict standards regarding who should be tested and when. A research infrastructure needs to be established whose purpose is to determine whether asymptomatic individuals with positive blood tests eventually develop clinical Alzheimer’s and whether anti-amyloid therapies given to asymptomatic individuals prevent cognitive decline. The results from these studies should then be evaluated by an impartial organization, such as the U.S. Preventive Services Taskforce, to establish guidelines on the use of blood-based biomarkers for screening in asymptomatic individuals. Meanwhile, primary care providers, geriatricians, and neurologists need to be ready to educate their patients on their potential benefits and limitations.
As we enter this new era of Alzheimer’s diagnostics and therapeutics, we must be careful to balance the power of these tools with their risks and downstream costs. The real-world implementation of blood-based biomarkers will require close collaboration between manufacturers, professional organizations, patient advocacy groups, and governmental entities to ensure they are provided economically and equitably. Only through a careful and methodical approach to their integration into the health care ecosystem will the full potential of these technologies be realized.
Naveen Reddy is a health policy fellow and neurologist at the University of California, San Francisco. Kristine Yaffe is the vice chair of psychiatry, neurology, and epidemiology at UCSF and the director of the Center for Population Brain Health at UCSF.