GreyMatters
Educational articles, BetterBrain resources, latest in brain health, and news about us. Written for you, with expertise (and love).
The Rise of Amyloid Blood Tests
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, PrecivityAD21, 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.
Final Thoughts
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.
Update April 19, 2024
Roche, in collaboration with Eli Lilly, has launched the Elecsys pTau-2172 blood test, which has recently received breakthrough device designation from the FDA. This means it was recognized as an effective tool for diagnosis, and is a critical milestone in how we identify Alzheimer's Disease. This test targets the tau protein pTau-217 and has the unique ability to distinguish AD from other neurodegenerative diseases. This is particularly important given that clinical AD diagnoses often lack sensitivity and specificity. It’s all the more since over half of patients with cognitive impairment remain undiagnosed or incorrectly diagnosed. This advancement promises to enhance early diagnostic accuracy and significantly improve intervention strategies for AD, particularly as global dementia figures are projected to rise sharply by 2050. pTau-217 is now available as an add-on service with BetterBrain.
Get immediate insights with a 3 minute assessment
Start now.png)
GreyMatters
Should you get tested for APOE4?
Chance are, you know someone who has tested for their APOE genotype. With the advent of consumer genotyping companies such as 23andme, genetic testing for Alzheimer's risk has become increasingly accessible, with the APOE4 gene variant taking center stage in the discussion. The question that many people are asking is: Should I get tested for APOE4? This article aims to provide a balanced perspective, detailing the pros and cons to help you make an informed decision.
What Is APOE4?
The APOE gene produces a protein essential for fat metabolism and is involved in brain cell repair. There are three main variants of this gene—APOE2, APOE3, and APOE4—with the APOE4 variant being strongly associated with an increased risk of developing Alzheimer's disease. While having this gene variant doesn't guarantee that you'll develop Alzheimer's, it can significantly elevate your risk. 20-25% of people have 1 copy of APOE4, conferring a 2-3X increase in Alzheimer's risk, while 2-3% of people have 2 copies, which implies an 8-10X increase in risk.
Advantages of APOE4 Testing
Empowers You to Make Informed Choices
Perhaps the most compelling reason for getting tested is the ability to make informed decisions about your health. There are specific recommendations for those carrying APOE4 such as significantly increasing DHA consumption given impaired absorption. Additionally, research suggests that APOE4 carriers get even more benefit from a range of interventions than non-carriers. In fact, some experts suggest that by applying the right interventions, you can completely mitigate the impact of having a copy of APOE4.
Opens opportunities for clinical trials and futures therapies
There is a significant research focus on APOE4 and potential pharmacological approaches to mitigating the associated risk. Testing may open up avenues for participating in such trials. Furthermore, as therapies get approved in the future for APOE4 carriers, you'll be well positioned to take advantage.
Offers Information for Family Planning
Your genetic makeup doesn't just affect you; it could also be informative for your family members. Given the heritability of the gene, knowing that you carry the APOE4 variant could give valuable insights into your relatives such as parents who may be at higher risk for developing dementia.
Drawbacks of APOE4 Testing
Carries Emotional and Psychological Weight
Although APOE4 is simply a risk factor and is far from being deterministic, finding out that you're at higher risk for Alzheimer's can be emotionally taxing. While the REVEAL study1 showed that disclosing ApoE4 status did not cause clinically significant anxiety or depression after 6 month follow up, responses are of course very individualized. Before taking the test, consider whether you're emotionally prepared for the results.
Doesn't Guarantee Prevention or Cure
At present, there is no cure for Alzheimer's. Knowing you have the APOE4 gene can offer a sense of urgency to adopt preventive measures, but it doesn't guarantee that you'll be able to ward off the disease.
Raises Ethical and Privacy Concerns
Genetic testing often brings up privacy issues. There's always the risk of data leaks or misuse by third parties, including insurance companies, even though laws exist to prevent genetic discrimination (e.g., GINA for health insurance). Be aware of these concerns when contemplating testing.
The Decision is Yours to Make
Choosing whether to undergo APOE4 testing is a deeply personal decision that should be based on multiple factors, including your emotional readiness, family history, and the current state of your cognitive health. Regardless of your decision, remember that the genetics are just one piece of a very complicated puzzle.