Study Offers New Insights into Alzheimer's Disease Biomarkers

As of November 14, 2024, the European Medicines Agency (EMA) has recommended, for the first time, a drug aimed at slowing the progression of Alzheimer's disease (AD). This marks a significant milestone and emphasizes the growing need for screening tests capable of identifying individuals in the early, asymptomatic stages of the disease—before irreversible damage occurs. In AD, tau proteins in the brain play a crucial role. Typically, these proteins help stabilize structures within brain cells, but in AD, they undergo abnormal changes (phosphorylation) and begin to aggregate. This abnormal clustering impairs the function of brain cells, leading to their eventual death. Blood-based tests are emerging as promising biomarker candidates, showing high accuracy in research cohorts. However, the relationship between plasma biomarker levels and the underlying pathology of AD—and how these results align with the biological changes and stages monitored by diagnostic tools used in clinical settings—remains unclear. Researchers have now worked to address these questions in a study published in eBioMedicine.

Previous research on plasma biomarkers has predominantly focused on well-controlled, research-based cohorts, where patients are selected based on specific criteria to ensure consistency. While this approach is essential for maintaining homogeneity, increasing statistical power, and controlling confounding factors, the next phase of biomarker validation requires real-world evidence to enhance the interpretability and relevance of these tests in broader populations. In this study, researchers at Karolinska Institutet (Stockholm, Sweden) analyzed data from a memory clinic cohort, exploring plasma biomarker levels in relation to standard diagnostic tests and the biological stages of AD. The cohort included a diverse group of patients with various pathologies, all of whom sought medical care at Karolinska University Hospital due to memory issues.

The study revealed that all tested plasma biomarkers (with the exception of NfL) were linked to the accumulation of misfolded amyloid in the brain, underscoring the role of amyloid in tau phosphorylation. Among the biomarkers assessed, only plasma levels of pTau217 were strongly associated with clinical variables, while over 70% of the variation in other plasma biomarkers remained unexplained. This research offers a deeper understanding of the complex relationships between novel plasma biomarkers and existing diagnostic tools. The researchers hope that these insights will facilitate the development of early diagnostic markers, ultimately leading to more timely treatments for Alzheimer's disease in the future.

“These findings are in line with the other recent reports on this topic, and add to the emerging body of evidence that plasma pTau217 is a dual marker of amyloid and tau pathology,” said Dr. Marina Bluma, postdoctoral fellow at the Department of Neurobiology, Care Sciences and Society. "Unlike these biomarkers, increased NfL levels were more indicative of brain atrophy and older age."

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