Blood Tests for Alzheimer’s Disease Are Not Far Off

Why are blood tests for Alzheimer’s disease important?

Posted Sep 14, 2020

The development of blood tests to determine various stages of pre-symptomatic Alzheimer’s disease is rapidly advancing. It is highly likely that such tests will become available within a few years. Why is this important?

Beta-amyloid and phosphorylated tau are two proteins thought to be directly involved in causing symptoms of Alzheimer’s disease. Each of these proteins forms clumps in the brain that can be visualized with positron emission tomography (PET), a specific type of medical imaging. In addition, these proteins can be measured in the cerebrospinal fluid (CSF) that bathes the brain and spinal cord. A sample of this fluid can be obtained by performing a lumbar puncture, a brief procedure requiring a trained specialist. Both PET imaging and lumbar punctures are expensive and time-consuming.

Recently, methods have been developed to measure components of amyloid in blood that accurately reflect the amount of amyloid in CSF. More recently, methods have been developed to measure specific forms of abnormal tau in blood that reflect the accumulation of these forms of tau in CSF. These measurements of amyloid and specific forms of abnormal tau in blood appear to reflect changes that are specifically related to the underlying processes resulting in Alzheimer’s disease.

Changes in blood levels of amyloid due to Alzheimer’s disease can be detected 20 or more years prior to clinical manifestations of the illness. Changes in blood levels of certain forms of abnormal tau start to occur shortly after the amyloid changes while other forms of abnormal tau increase several years later, but still before symptoms become evident. Finally, as discussed in an earlier post, blood levels of another protein called neurofilament light chain (NfL) increase at the time of actual destruction of brain structures. However, increases in NfL occur with any type of brain degeneration; thus, increases in NfL are not specific to Alzheimer’s disease.

It is likely that a blood test measuring forms of amyloid, tau, NfL, and perhaps other chemicals can lead to a reasonably accurate determination of how advanced the pre-symptomatic phase of the illness is and when symptoms may become evident. This is important because treatments will likely differ depending on the stage of the disease. Drugs are currently being developed that interfere with the accumulation of amyloid and tau. In addition, it is likely that inflammatory responses occur at different pre-symptomatic stages of the illness, and targeting these responses with medications may prove helpful.

Blood tests will also be helpful in advancing Alzheimer’s disease research. Determining persons who are in various pre-symptomatic stages of this illness with a blood test will make it much easier to recruit such individuals into research projects and treatment trials.

The ability to utilize a blood test to identify people in very early, pre-symptomatic stages of Alzheimer’s disease is only a few years away. This will aid in developing treatments for specific stages of pre-symptomatic and perhaps symptomatic illness. It is not unreasonable to believe that treatments that delay or perhaps prevent and/or reverse symptoms of this devastating disease will be developed during the coming decade.

This column was written by Eugene Rubin MD, Ph.D., and Charles Zorumski MD.

References

Bateman, R.J., Barthelemy, N.R., & Horie, K. (2020 Mar). Another step forward in blood-based diagnostics for Alzheimer's disease. Nat Med. 26(3): 314-316.

Barthelemy, N.R., Horie, K., Sato, C., & Bateman, R.J. (2020). Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer’s disease. J. Exp. Med. https://doi.org/10.1084/jem.20200861 [epub ahead of print].