BlueCross BlueShield of Tennessee Medical Policy Manual

Biochemical Markers for Alzheimer’s Disease


The clinical diagnosis of Alzheimer 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 disease.

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




Evidence to support testing for AD-related biomarkers is lacking. For the diagnosis of AD, evidence does not demonstrate incremental improvement in diagnostic accuracy over clinical testing.


Bateman, R. J., Xiong, C., Benzinger, T. L. S., Fagan, A. M., Goate, A., Fox, N. C, et al. (2012). Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. New England Journal of Medicine, 367 (9), 795-804. (Level 2 evidence)

BlueCross BlueShield Association. Medical Policy Reference Manual. (12:2016). Cerebrospinal fluid and urinary biomarkers of Alzheimer disease (2.04.14). Retrieved June 23, 2017 from BlueWeb. (42 articles and/or guidelines reviewed)

Jack, C., Albert, M., Knopman, G., Sperling, R., Carrillo, M., Thies, B. et al. (2011). Introduction to the recommendations from the National Institute on Aging and the Alzheimer’s Association workgroup on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association, 7 (3), 257-262. (Level 4 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)

Miller, A., Begley, E., Coen, R., Doyle, M., Dunne, J., Hutchinson, S. (2016). Clinical consensus guidelines on the application of cerebrospinal fluid biomarkers for Alzheimer’s disease diagnosis: recommendations of the Irish network for biomarkers in neurodegeneration. Irish Medical Journal, 109 (10), 483. (Level 2 evidence)

National Institute on Aging & Alzheimer’s Association. (2011). The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute of Aging - Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Retrieved June 26, 2017 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, 2017 Jun 19:1-9. Doi: 10.1080/14737175.2017.1341311. [Epub ahead of print]. Abstract retrieved June 26, 2017 from PubMed database.




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