A hand in a blue rubber glove holding a blood test tube labelled Alzheimers...

Article • Detection of neurodegenerative condition

Developing blood biomarkers to diagnose Alzheimer’s disease

There is no known cure for Alzheimer’s disease (AD), although prescription drug-based treatments that can slow AD progression in some patients are starting to enter clinical use. Biomarkers, quantifiable characteristics of biological processes or pathological conditions of the body, are making it possible to help identify and measure the presence and extent of AD and its degenerative progression.

Report: Cynthia E. Keen

A blood plasma biomarker test received international media attention in July 2024 when results of a large clinical trial showed it to be 91% accurate in diagnosing AD in patients who had been clinically evaluated and diagnosed, compared to 73% by dementia specialists and 61% by primary care physicians. The study involved 17 primary and secondary care centres in Sweden treating 1,213 patients over 65 years old experiencing symptoms ranging from subjective cognitive decline to dementia. Half had pathologically confirmed AD.¹

The significance of this research becomes clear in light of experts predicting that in 2025, 10 million people will develop Alzheimer’s. Leading organisation Alzheimer’s Disease International (ADI) further estimates that the disease will escalate from 55 million cases worldwide to 78 million by 2030 and more than 139 million cases by 2050.²

Benefits for diagnostics and research

When blood biomarker tests for AD do become clinically available, unlike the current testing methods of expensive positron electron tomography (PET) imaging scans and invasive lumbar spine puncture for a cerebrospinal fluid test, they will offer many advantages. These are expected to be widespread availability, low cost, easy acquisition from patients, and accurate laboratory analysis. But they are not going to be a commonplace screening tool soon.

Many clinical research challenges await. Sebastian Palmqvist, MD, PhD, Associate Professor in the Clinical Memory Research Unit at Lund University and principal investigator of the Swedish study, advised during a JAMA Medical News podcast that the test is not a stand-alone diagnostic AD test, but rather something that should accompany the standard clinical evaluation. However, he emphasized that 'you need biomarker tools to accurately identify AD, because the clinical symptoms aren't specific for that disease and can be caused by many other ideologies.³

The lack of biomarkers to track therapeutic response has raised questions about whether drugs reach their targets and produce the expected biological effects
Tharick A. Pascoala, Cristiano S. Aguzzoli, Firoza Z. Lussier et al.

The development of blood biomarker tests will greatly aid drug-related clinical trials. In a recent review on this topic, lead author Tharick A. Pascoal, MD, PhD, an Associate Professor of Psychiatry and Neurology at the University of Pittsburgh, along with an international team of co-authors, state that 'the importance of biomarkers in drug development is growing exponentially' and that they 'are expected to serve a wide range of contexts of use in clinical trials focusing on AD and other dementias.'⁴

'The lack of biomarkers for population selection [of early clinical trials targeting Amyloid-beta] has raised the possibility that their negative results could be because other brain pathologies, unaffected by the drugs being studied, were causing symptoms in many participants,' they write. 'Furthermore, the lack of biomarkers to track therapeutic response has raised questions about whether drugs reach their targets and produce the expected biological effects. The lessons learned from these clinical trials have highlighted that it is imperative to use biomarkers for more informative drug development in the field of AD.'

Article • Promising, but in need of further validation

Implementation challenges of blood biomarkers for Alzheimer’s disease

Blood-based biomarker (BBB) tests may represent the best weapon to combat the soaring rates of Alzheimer’s disease (AD) throughout the world. Existing clinically validated tests are currently deployed to facilitate diagnosis, to monitor disease and effectiveness of treatments, to quantify progression, and to determine if a patient is appropriate for treatment or participation in a clinical…

Categories and complexities

Blood biomarkers for AD do not have a single category, but three. The first class includes biomarkers associated with the presence of beta-Amyloid plaques and p-tau tangles, both of which are classic pathological hallmarks. The second class is associated with neuronal loss, neurodegeneration, or synaptic degeneration. The third class includes processes related to neuroinflammation related to glial cells.

The US Food and Drug Administration and National Institutes of Health created a FDA-NIH Biomarker Working Group in 2016, which defined and established nine types of biomarkers. These are categorized in diagnostic, predictive, prognostic, susceptibility, response, monitoring, and safety categories.⁵ Diagnostic biomarkers are most publicly associated with blood laboratory tests being used in clinical trials and in development.

Better diagnostics lead to increased need for care

Assuming that blood biomarker tests become clinically approved and low in cost, what then? Commenting about the accuracy of the blood plasma test used in the Swedish clinical trial in a JAMA editorial, dementia specialist physicians from Australia and the United States point out the need for a significant increase in nurse practitioners, nurses, and care navigators.⁶

Lead author Stephen Salloway, MD, of the Departments of Psychiatry and Neurology of Warren Alpert Medical School of Brown University in Providence, Rhode Island, and co-authors write, 'Advances in the diagnosis and treatment of Alzheimer disease will require important changes to care models. It will not be possible to provide high-quality dementia care in a new molecular era within the already overburdened practice settings without providing additional resources and staffing.’

This by itself is a huge challenge, and is not being achieved to effectively deal with the needs of today’s AD patients and their caregivers, even though an estimated $1.3 trillion is being spent, according to ADI.

Profile:

Sebastian Palmqvist, MD, PhD, is Associate Professor in the Clinical Memory Research Unit at Lund University. He also is a Consultant Neurologist at Skåne University Hospital in Malmö, Sweden. Palmqvist is principal investigator of ADetect, a 24 month long AD detection study launched in January 2024, and a research participant in Lund University ongoing EDAP (early prognostics of Alzheimer’s disease) project.

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06.03.2025