BlueCross BlueShield of Tennessee Medical Policy Manual

Biochemical Markers for Alzheimer’s Disease


The clinical diagnosis of Alzheimer’s disease (AD) focuses on the exclusion of other causes of dementia. Because diagnosis of AD can be difficult, there has been considerable interest in identifying an accurate laboratory test for AD, particularly for use early in the course of the disease.

Several cerebrospinal fluid (CSF) peptide markers and urine markers have been investigated as possible predictors of AD and include the following:

ADmark® CSF Analysis tests can be used to detect phosphorylated tau protein, total tau protein and amyloid-β peptide 1-42 peptide in cerebrospinal fluid. AlzheimAlert™ tests can be used to detect neural thread protein in urine or cerebrospinal fluid.



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Evidence for the use of biochemical markers to diagnose Alzheimer’s disease does not demonstrate incremental improvement in diagnostic accuracy over clinical testing.


Alzheimer’s Association. (2019). Earlier diagnosis. Retrieved June 4, 2019 from

BlueCross BlueShield Association. Evidence Positioning System. (1:2021). Evaluation of biomarkers of Alzheimer disease (2.04.14). Retrieved February 5, 2021 from (36 articles and/or guidelines reviewed)

Herukka, S.K., Simonsen, A.H., Andreasen, N., Baldeiras, I., Bjerke, M., Blennow, K., et al. (2017). Recommendations for cerebrospinal fluid Alzheimer’s disease biomarkers in the diagnostic evaluation of mild cognitive impairment. Alzheimer’s & Dementia, 13, 285-295. (Level 1 evidence)

McKhann, G., Knopman, D., Chertkow, H., Hyman, B., Jack, C., Kawas, C., et al. (2011). The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging and the Alzheimer’s Association workgroup. Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association, 7 (3), 263-269. (Level 2 evidence)

Mroczko, B., Groblewska, M., & Litman-Zawadzka, A. (2019). The role of protein misfolding and Tau oligomers (TauOs) in Alzheimer’s disease (AD). International Journal of Molecular Sciences, 20 (19), 4661. (Level 3 evidence)

National Institutes of Health. National Institute on Aging. (2019). Biomarkers for dementia detection and research. Retrieved June 4, 2019 from

Olsson, B., Schott, J., Blennow, K., & Zetterberg, H. (2017). The use of cerebrospinal fluid biomarkers to measure change in neurodegeneration in Alzheimer’s disease clinical trials. Expert Review of Neurotherapeutics, 17 (8), 767-775. Abstract retrieved June 26, 2017 from PubMed database.

Rosa, M.I., Perucchi, J., Medeiros, L.R., Fernandes, B., Fernandes, D., & Silva, B.R. (2014). Accuracy of cerebrospinal fluid (Aβ(1-42) for Alzheimer’s disease diagnosis: a systematic review and meta-analysis. Journal of Alzheimer’s Disease, 40 (2), 443-454. Abstract retrieved June 5, 2018 from PubMed database.

United States Preventive Services Task Force. (2020). Screening for cognitive impairment in older adults. Retrieved February 5, 2021 from

Zhang, J., Zhang, C.H., Li, R.J., Lin, X.L., Chen, Y.D., Gao, H.Q., & Shi, S.L. (2014). Accuracy of urinary AD7c-NTP for diagnosing Alzheimer’s disease: a systematic review and meta-analysis. Journal of Alzheimer’s Disease, 40 (1), 153-159. Abstract retrieved June 5, 2018 from PubMed database.




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