Alzheimer’s disease (AD) is the leading cause of dementia, accounting for approximately 60-80% of all cases. Like other forms of dementia, AD is an incurable neurodegenerative condition that comes with progressive memory and language loss, confusion, mood changes, and severe cognitive decline over time.

According to the Alzheimer’s Association, about 1 in 9 adults over the age of 65 in the United States has AD. This equates to about 7 million Americans currently living with AD, and this number is expected to reach 13.8 million by 2060. The lifetime risk is alarming; a 45-year-old woman faces a 1 in 5 chance of developing AD during her lifetime, while the risk for men is 1 in 10. The aging global population, increases in life expectancy, and improvements in diagnosis are among the major reasons for the rise in AD prevalence over the last few decades (1).

Early detection of Alzheimer’s is vital for maximum treatment benefit

Despite decades of research to identify ‘the’ cause of AD, it is now widely accepted to be multifactorial with both genetic and environmental factors contributing to its onset and progression. The amyloid cascade hypothesis, which centers on the accumulation of abnormal amyloid beta (Aß) protein plaques as a key driver of neurodegeneration in AD, has guided most drug discovery efforts to develop disease-modifying therapies that can slow or alter disease progression.

Two anti-amyloid monoclonal antibodies, donanemab and lecanemab, approved by the United States FDA in 2023 and 2024, respectively, are now available to treat early-stage AD. These work by targeting amyloid plaques in the brain, but are only effective very early in disease, making it essential to detect AD before significant cognitive decline occurs.

According to the Alzheimer’s Association, studies have found that 50% or more of patients with AD are not diagnosed until the moderate or advanced stage of disease, at which point they cannot benefit from the new therapies. This highlights the urgent need for scalable early detection strategies including blood-based biomarkers to allow timely intervention and maximize the impact of emerging therapies.

Blood biomarkers for Alzheimer’s disease

One of the most striking discoveries in Alzheimer’s research is that the disease begins silently in the brain decades before symptoms appear, with biomarker and autopsy studies showing that amyloid and tau accumulation can start 20 years or more before memory loss, confusion, or other signs of dementia. This prolonged preclinical window represents an important opportunity for earlier detection, which blood-based biomarkers are now making possible.

Among the biomarkers studied, p-tau217 has shown strong potential for detecting early signs of AD. Other phosphorylated tau isoforms, such as p-tau181 and p-tau231, are also under investigation, but so far, p-tau217 has consistently shown the greatest sensitivity and specificity for early detection of AD.

In May of this year, the FDA approved the Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio test as the first in vitro diagnostic blood test for AD. Lumipulse measures the ratio of phospho-tau and beta-amyloid to infer if AD is likely present. This test is much less invasive than PET scanning or lumbar puncture (which are conventionally used to diagnose AD) since it only requires a single blood draw. While Lumipulse represents a major step forward in accessible AD diagnostics, its current indication is limited to adults aged 55 and older who already exhibit symptoms. As a result, it does little to address the urgent challenge of identifying patients in the very early, presymptomatic stages of AD, i.e., the stage at which emerging therapies are likely to have the greatest benefit.

Beyond the Lumipulse test developed by Fujirebio, other companies such as Quanterix and Alamar are advancing highly sensitive immunoassays to detect p-tau217 in the blood and cerebrospinal fluid. Early studies show that these technologies can also identify Alzheimer’s-related changes, supporting the broader expansion p-tau217 from research into routine clinical use (2).

If biomarkers exist, why don’t we screen more broadly for Alzheimer’s?

Despite the intensifying global burden of AD, no population-wide screening programs exist, even though early intervention and timely treatment could reduce long-term healthcare costs and improve patient outcomes.

Several factors may explain why AD screening is so far limited, including:

• Public healthcare systems may not yet have the infrastructure to manage the scale of population-wide screening, which would require mass testing, data tracking, and follow-up for millions of people. These challenges are confounded by the fact that the only FDA-approved blood biomarker test, Lumipulse G pTau217/β-amyloid 1-42 Plasma Ratio, has a narrow scope. Because its use is restricted to symptomatic adults 55 years and older, many patients are still diagnosed too late to benefit from treatment.
• Limitations of available treatments may create barriers to broad screening. For example, donanemab and lecanemab may not be suitable for all AD patients. In particular, carriers of the APOE ε4 gene variant are at higher risk of developing amyloid-related imaging abnormalities (ARIA), a serious side effect, which is why genetic testing and regular MRI monitoring are recommended before and during treatment. Other safety concerns include infusion-related reactions, allergic responses, headaches, and falls.
• Ethical considerations. Donanemab and lecanemab are still very new and it is not known if and to what extent they can delay symptom onset if started in the presymptomatic stage of disease. At the same time, broad screening could identify millions of people who may never go on to develop Alzheimer’s symptoms, or who may face many years of anxiety before symptoms emerge. For these individuals, screening would cause more harm than good. Such considerations are likely to influence policy and clinical practice surrounding AD screening for many years to come.
• Cost is a major barrier. Even when patients are eligible for and can tolerate the newest therapies, their high cost and need for regular monitoring creates access issues, so not every patient who could potentially benefit would be able to access the treatments.

Early-stage testing could still transform detection and treatment

Despite the limitations outlined above, early detection of AD can make a difference for those who choose to be tested, especially given that more than half of patients are still diagnosed too late to benefit from the available therapies (Alzheimer’s Association, 2024).

Self-sampling technologies such as volumetric dried blood or plasma microsampling-based testing could help overcome some of the barriers to AD screening by increasing accessibility outside of traditional clinical settings. The possibility for self-sampling can reduce or eliminate initial barriers, such as geography and mobility, that might deter asymptomatic people from testing, thereby enabling broader participation in early detection and timely treatment.

Studies so far have shown that biomarker detection from dried microsamples correlates extremely well with venous blood-based measurements, and dried samples are stable at room temperature for at least 6 months. Recent advances also show the potential of combining microsampling with high-throughput proteomics to capture a full panel of Alzheimer’s-related biomarkers, including multiple phosphorylated tau isoforms, Aβ42/40, and neurofilament light (3). This could expand screening beyond p-tau217 alone and provide a more comprehensive and accurate picture of disease risk.

Earlier treatment would not only improve patient outcomes but could also lead to major cost savings by prolonging the time between symptom onset and cognitive decline, thereby reducing the need for intensive care in aging populations. With new therapies in rapid development, the demand and motivation for early screening are likely to grow, paving the way for broader adoption in both private and eventually public healthcare systems.

References:

1. Alzheimer’s Association. 2025 Alzheimer’s disease facts and figures. Alzheimer’s Dement. 2025;21(3): e700640.
2. Chen Y, Albert AL, Sehrawat A, et al. Equivalence of plasma and serum for clinical measurement of p-tau217: comparative analyses of four blood-based assays. medRxiv [Preprint]. 2024 Dec 28:2024.12.26.24319657. Update in: J Neurochem. 2025 Jul;169(7):e70114.
3. Huber H, Blennow K, Zetterberg H, et al. Biomarkers of Alzheimer’s disease and neurodegeneration in dried blood spots-A new collection method for remote settings. Alzheimers Dement. 2024 Apr;20(4):2340-2352.