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Center for Cognitive Health

Biomarker Assessments: The Future of Alzheimer’s Diagnosis

The prevalence of Alzheimer’s Disease (AD) reinforces the need for reliable early detection and intervention. Treatment is most effective early in the disease. Thus, there is a critical need for approaches that can identify AD at its earliest stages. Clinical symptoms are the primary method of diagnosis but only emerge after decades of disease progression. Biomarker assessments have emerged as a promising choice for early diagnosis and understanding of disease progression.

Biomarker assessments have been used for over 20 years in research studies but are now becoming more available for clinical diagnosis.

Biomarkers detect amyloidosis, tauopathy, neuroinflammation, and neurodegeneration and can be obtained through cerebrospinal fluid (CSF), neuroimaging, and most recently, blood tests. The use of CSF and neuroimaging can be limited due to cost, invasiveness, and accessibility. While blood-based biomarker tests are still in the early stages, some assays are proving to be a formidable alternative holding promise for more affordable and widespread screening and monitoring of AD.

To further increase the efficacy of these biomarker assessments, on May 6th, 2024, the FDA announced that laboratory diagnostic tests for diseases such as AD will be more strictly regulated, similar to medical devices. Beginning July 5th, these tests will need to show greater evidence of accuracy and report adverse events. While this could have negative impacts on test costs, it will ensure greater accuracy and patient safety.

Two recent longitudinal studies have confirmed a previous understanding of the progression of AD and resulted in the same conclusions. In a study by Jianping Jia and colleagues, participants were tracked over twenty years. Researchers identified those who developed AD and compared the sub-group of those individuals to cognitively normal participants assessing CSF concentrations, cognitive testing scores, and neuroimaging. They examined the progression from presymptomatic amyloid positivity to the presence of mild symptoms, finding biomarker differences nearly twenty years before symptom onset. Increased amyloid levels were the first noticeable changes followed by increased tau levels, neuroinflammation, and neurodegeneration. Cognitive changes were the last to be detected.

Suzanne Schindler and colleagues developed an amyloid clock to explain the trajectory of the disease, confirmed by longitudinal biomarker studies of diverse populations. When the accumulation of amyloid levels in the brain increases beyond normal production, it sets off the ‘clock’, triggering other biological cascades with symptom onset about twenty years later.

            As noted, blood-based biomarker assessments are emerging. Various assays have been developed as potential markers of AD including neurofilament light chain (NfL), plasma beta-amyloid levels, and phosphorylated tau protein (p-tau). Nfl assays measure proteins in degenerating nerve cells that correlate to cell death but may not necessarily be specific to AD pathology. Plasma amyloid beta ratios evaluate the balance between different forms of amyloid beta. The ratio, formerly referred to as the onset of the amyloid clock, currently is used clinically to confirm AD diagnosis. Amyloid beta can be a very early indicator of AD but does not correlate to cognitive decline and disease progression as does neurofibrillary tangles (NFTs). P-tau assays measure the abnormal phosphorylation of tau protein from NFTs. P-tau217 might offer greater accuracy in diagnosis than p-tau181 as studies indicate p-tau217 levels rise earlier relative to disease progression and demonstrate better precision in distinguishing AD from other neurodegenerative disorders. A new observational clinical trial by Eli Lilly and Company will utilize a blood-based biomarker test for P-tau 217 (Sp-X P-tau217). The purpose of the study is to assess the result’s impact on physician treatment plans. The Center for Cognitive Health is now enrolling for this trial. If you are interested, please give us a call at (503) 207-2066 or fill out our submission form to schedule a free phone screen here.

Early detection using biomarkers allows patients more control over their health and treatment. Ongoing biomarker research will allow a better understanding of individual differences in AD and subgroup treatment differences.


FDA will regulate diagnostic tests. Yes, those for Alzheimer’s, too. (10 May 2024). ALZFORUM. https://www.alzforum.org/news/community-news/fda-will-regulate-diagnostic-tests-yes-those-alzheimers-too.

From St. Louis to Beijing: AD biomarkers change similarly before symptoms. (29 February 2024). ALZFORUM. https://www.alzforum.org/news/research-news/st-louis-beijing-ad-biomarkers-change-similarly-symptoms.

Jia, J., Ning, Y., Chen, M., Wang, S., Yang, H., Li, F., … & Wang, S. (2024). Biomarker changes during 20 years preceding Alzheimer’s Disease. New England Journal of Medicine390(8), 712-722.

Li, Y., Yen, D., Hendrix, R. D., Gordon, B. A., Dlamini, S., Barthélemy, N. R., … & Schindler, S. E. (2024). Timing of biomarker changes in sporadic Alzheimer’s Disease in estimated years from symptom onset. Annals of Neurology, 95(5), 951-965.

Pais, M. V., Forlenza, O. V., & Diniz, B. S. (2023). Plasma biomarkers of Alzheimer’s disease: a review of available assays, recent developments, and implications for clinical practice. Journal of Alzheimer’s Disease Reports, 7(1): 355-380.