Preparing Your Lab for Blood-Based Alzheimer’s Disease Testing

Blood-based diagnostics for Alzheimer’s disease and other neurological conditions could be here sooner than you think.

By Arindam Ghosh, MBBS, PhD

Summary:

The potential for blood-based testing to diagnose Alzheimer’s disease is on the horizon, signaling a significant shift in the diagnostic landscape and necessitating preparation from clinical stakeholders and labs.

Takeaways:

1. Current Challenges: Diagnosing Alzheimer’s disease involves a complex, multi-step process including medical history, physical exams, cognitive tests, imaging, and sometimes invasive procedures like cerebrospinal fluid analysis.
2. Emerging Solutions: New blood tests measuring biomarkers like amyloid beta, neurofilament light chain, and phosphorylated tau protein are less invasive and promise to make Alzheimer’s diagnosis more accessible and convenient.
3. Preparation Steps: Labs should familiarize themselves with the evolving diagnostic landscape, evaluate their current capabilities, and plan for scaling up to accommodate blood-based biomarker assays, ensuring they can meet future diagnostic demands.

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Change is coming for the way we diagnose Alzheimer’s disease. Your clinical stakeholders are focused on it. Your patients are asking for it. And now, the possibility of blood-based testing could soon be within reach. Now is the time to familiarize yourself with the current diagnostic landscape and begin charting your path to the future.

Identifying Alzheimer’s Disease Pathology: A Complex and Often Inaccessible Process

Current testing for AD relies heavily on clinical examination. The diagnostic process can be time-consuming and intricate, involving multiple steps, including:

• Full medical history with the provider asking about symptoms, medical history, medications, and any family history of dementia or Alzheimer’s disease
• Physical exam to help rule out other potential causes of cognitive impairment and assess overall health
• Cognitive tests like the Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA) to evaluate memory, thinking, and other cognitive functions
• MRI or CT scans to help identify structural changes in the brain, such as shrinkage of certain brain regions or the presence of abnormalities like amyloid plaques and tau tangles
• Blood tests to rule out other conditions that can cause cognitive decline, such as thyroid dysfunction, vitamin deficiencies, or infections
• More in-depth neuropsychological assessment of cognitive functions, memory, language, and other mental abilities—often conducted by a neuropsychologist
• Cerebrospinal fluid analysis via lumbar puncture to analyze levels of amyloid beta and tau proteins in the cerebrospinal fluid
• Genetic testing, especially for individuals with a family history of early-onset Alzheimer’s disease

While prospects are growing brighter every day, today’s path to Alzheimer’s disease diagnosis remains a long and complex one. However, blood-based biomarkers could forever change how neurodegenerative diseases are investigated, diagnosed, and monitored. What could this mean for the future of your lab?

Labs Could Soon Play Leading Roles in Alzheimer’s Disease Testing

Rather than relying on invasive and often hard-to-access methods like CSF testing and PET scans, the future of Alzheimer’s testing could very well center around the lab. Several new and emerging blood tests aim to detect Alzheimer’s biomarkers in a less invasive and more accessible way.

Some of the promising blood tests include:

• Plasma amyloid beta (Aβ): Some blood tests measure levels of amyloid beta in the blood, which reflect the accumulation of amyloid plaques in the brain. Elevated levels of specific forms of amyloid beta in the blood (e.g., Aβ₄₂) may be associated with an increased risk of developing Alzheimer’s disease.¹
• Neurofilament light chain (NfL): Blood tests that measure levels of NfL, a protein released into the blood following neuronal damage, may help detect neurodegeneration in the brain, which is a key feature of Alzheimer’s disease. Elevated NfL levels in the blood have been associated with cognitive decline and Alzheimer’s disease progression.²
• Phosphorylated Tau protein (p-Tau): Blood tests that measure levels of phosphorylated Tau protein are emerging key biomarkers for the diagnosis and prognosis of Alzheimer’s disease. A pathologic hallmark of Alzheimer’s is the abnormal phosphorylation of tau which leads to tau aggregation. This aggregation of hyperphosphorylated tau in neurons can cause neuronal damage and synaptic loss in the brain. Elevated p-tau levels in the blood have been linked to cognitive impairment and Alzheimer’s disease.³

Benefits of Blood-Based Testing

Blood-based testing could open the door to many new possibilities for diagnosing Alzheimer’s disease and other forms of dementia. It could also create many opportunities for the lab to play a leading role.

The benefits are plentiful. Blood tests are less invasive and more convenient than procedures like lumbar punctures for CSF analysis. Blood tests can be easily performed in clinical settings and labs like yours, which could make them more widely available than CSF testing or brain imaging. Finally, blood tests that identify Alzheimer’s disease biomarkers could help providers identify individuals at risk of developing the disease or detect early stages of pathology before symptoms manifest.

Of course, there will be challenges as well. The accuracy of blood tests in detecting Alzheimer’s disease biomarkers may vary, and false positive or false negative results could occur.

Standardization of blood tests for Alzheimer’s disease biomarkers is still a work in progress, and variability in test methods and results could impact reliability. Finally, blood test results may need to be interpreted in conjunction with other clinical assessments and diagnostic tests to confirm a diagnosis of Alzheimer’s disease.

How Can You Start Preparing Now?

Fueled by epidemiological factors such as population growth, longer life expectancies, and the availability of novel therapeutics, we are facing a population that requires scalable, affordable, and easy-to-use testing in the core laboratory. While blood-based testing is not yet widely available, there are steps you can take today to help your lab prepare.

First, familiarize yourself with the evolving neurology landscape. Neurological testing may make up a small portion of your workload today—but that could change soon. Talk with your clinical partners about the most prevalent conditions they are seeing in your communities and get up to speed on the latest treatments and diagnostics in the research pipeline today.

Next, factor neurological testing into your future planning by evaluating your current capabilities. Few labs have the equipment and staffing it would take to handle blood-based Alzheimer’s testing at scale today—but there are steps you can take now to prepare. For example, do your analyzers run the blood-based biomarker assays that could hold such promise in testing for Alzheimer’s and other conditions? Could any part of your workflow be automated or made more efficient to help you scale up testing? If expanding your physical footprint isn’t an option, could you move to instruments that handle multiple types of tests? The sooner you begin asking these questions, the sooner you can be prepared to make a difference.

The Future Looks Bright

One thing is certain—new blood-based Alzheimer’s disease diagnostics are coming. These new tests promise to change the role labs play in diagnosing neurodegenerative diseases. Overall, blood tests for Alzheimer’s disease show promise for early detection, monitoring disease progression, and assessing response to treatment. If you want your lab to be ready, there’s no time like the present to start planning.

About the Author

Arindam Ghosh is director, medical & scientific affairs for Beckman Coulter.

References

1. Gabelle A et al. Plasma amyloid-β levels and prognosis in incident dementia cases of the 3-City Study. J Alzheimers Dis. 2013;33(2):381-91.
2. Lehmann et al. Blood Neurofilament Levels Predict Cognitive Decline across the Alzheimer’s Disease Continuum. Int J Mol Sci. 2023 Dec 11;24(24):17361.
3. Karikari et al. Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility. Nature Reviews Neurology volume 18, pages 400–418 (2022)