The Landscape of Alzheimer's Biomarkers
When it comes to assessing the risk of cardiovascular disease, we have straightforward biomarkers such as ApoB (LDL) and blood pressure which can predict risk fairly accurately. However, the realm of neurodegenerative diseases like Alzheimer's is a lot more messy. For years, researchers and clinicians have depended PET scans or cerebral spinal fluid (CSF) for analyzing biomarkers like amyloid and tau proteins. But these procedures are expensive ($5-10K in the case of PET) or invasive (CSF requires a lumbar puncture), making them impractical for widespread use.
Enter blood amyloid tests, a relatively new but promising diagnostic aimed at solving this problem.
What Are Blood Amyloid Tests and How Do They Work?
As the name suggests, these tests measure the concentration of various amyloid beta proteins in the blood (and sometimes tau as well) as a proxy for amyloid deposition in the brain. While the scientific community continues to debate whether amyloid pathology is a root cause of Alzheimer's disease or merely a symptom of other underlying brain pathologies, there is a clear association between the extent of amyloid presence in the brain and the manifestation of the disease.
One of the original commercially available tests was PrecivityAD by C2N. This test needs to be ordered by a physician and was designed to predict the likelihood of Alzheimer's Disease (AD) pathology by analyzing a few key factors:
- The ratio of two variants of amyloid beta proteins, specifically amyloid beta 42 and amyloid beta 40
- The ApoE variant of the patient
- The age of the individual
By amalgamating these variables, the test attempts to gauge the probability of a positive PET scan. While it's too early to draw any definitive conclusions, there are two primary reasons why looking at this data could be valuable:
- Comprehensive Risk Assessment: The test results can be used in combination with other factors like family history, genetics, metabolic health, vascular health and cognitive testing to assess the overall risk.
- Monitoring Interventions: The score could be used as a dynamic indicator to monitor the effectiveness of steps taken to mitigate Alzheimer's risk. If the score decreases, it suggests that the ratio of amyloid beta 42 to amyloid beta 40 has changed favorably and thus risk has been reduced.
Since then, C2N launched a second generation version of the tests, PrecivityAD2, which accounts for serum tau concentration for additional accuracy. In August of 2023, Quest launched a direct-to-consumer version of the test that does not require physician ordering. While the test is not quite as accurate as C2N in predicting a positive PET, it comes at a materially lower cost - $400 as of the date of this writing.
Applicability: Who Should Consider blood amyloid tests?
According to medical experts, the test should be reserved for those at high risk of developing Alzheimer's, as its sensitivity and specificity are still not entirely understood. The key term here is "pre-test probability." The higher the pre-test probability, the more reliable the test becomes in predicting a positive or negative outcome.
The emergence of amyloid (and tau) blood tests is an exciting development in the field of Alzheimer's research and prevention. Although not a complete solution, they do provide an additional layer of information that can potentially enhance our ability to serve people at risk of developing disease. As our grasp of amyloid biomarkers improves, these tests could become integral parts of a broader, more nuanced approach to diagnosis and risk assessment.