For decades, we have been trying to find out how to diagnose, let alone cure, Alzheimer’s. From expensive tests to long waiting times, some methods of diagnosis seem highly impractical. Is the solution truly just a few drops of blood?
Alzheimer’s disease is a progressive condition that results in the degeneration of brain cells and their connections, manifesting as memory loss. It is thought to stem from the abnormal buildup of beta-amyloid and tau proteins. Amyloid buildup forms plaque around neurons, whereas tau buildup forms tangles within neurons. Currently, there is no cure, only temporary treatments and brain exercises to delay the progression of the disease. Developing a treatment is difficult because not enough is known about the biology of Alzheimer's, despite nearly 10% of those 65 and older and 32% of those 85 and older having the disease [1]. We do not even know what causes the buildup of the proteins in the brain. Diagnosis is often delayed because the disease develops gradually and can only be detected when severe and noticeable neurodegenerative changes have occurred. Even when one does get tested for Alzheimer’s, the symptoms can mimic those of many other diseases, which complicates the diagnostic process [2]. Moreover, the current methods measuring Alzheimer’s disease before symptoms occur are through positron-emission tomography (PET) scans and cerebrospinal fluid (CSF) assays that measure protein presence. These methods are expensive, invasive, and inaccessible [3]. Over the course of the diagnostic process, the patient’s condition continues to escalate without proper treatment or attention.
C2N Diagnostics’ Precivity AD blood test, aimed at those 60 and older, has allowed for potentially more objective measures for Alzheimer’s. The blood test aims to measure brain amyloid protein levels and has been accurate in identifying status in 86% of patients. This can be compared to a 70% accuracy of symptomsbased tests. Though clinical diagnosis is still needed, this blood test would serve as an inexpensive and accessible tool to aid doctors and patients. Compared with current methods of diagnosing Alzheimer’s, the blood test is non-invasive and involves no radiation. The test generates an Amyloid Probability Score (APS) from a blood sample collected from an individual’s forearm. The probability score is then used to assess the likelihood of amyloid plaques in the brain. While a low APS score would provide the same information as a negative amyloid PET scan, a high APS score would provide the same information as a positive PET scan and indicate a high likelihood of amyloid plaques. Through coupling this result with clinical diagnosis, patients can receive treatment earlier to delay progression [4].
C2N is the first company to have developed a blood test for Alzheimer’s that is now available in most U.S. states. The price of the test is $1,250, which is quite expensive. Those who qualify for financial assistance will be charged between $25 and $400. C2N CEO Joel Braunstein states that decreasing this price is a high priority for the company, especially considering that health insurance companies do not currently pay for the test and that physician approval is needed [5].
This blood test is considered a great feat, as many had thought that the blood-brain barrier would make such biomarkers, like amyloid status, impossible to analyze because of their relative scarcity in the blood, but the high sensitivity of the blood test is able to address this issue.
Though this innovation is impressive, there are limitations that we must consider. The first criticism is that there is not yet enough data on this test for it to be commercially viable. Some key test results have not even been published. The second criticism is that it is not FDA approved. Heather Snyder, the Alzheimer’s Association Vice President of Medical & Scientific Relations, stated that no endorsement of the test will come from the organization until FDA approval is received [6]. These limitations mean that test results may not be generalizable or interpretable. Moreover, some researchers have indicated that biomarkers of tau proteins would be far more important, especially considering that they are better at distinguishing Alzheimer’s from other forms of dementia.
It seems as though this amyloid blood test has opened the door for development in tau blood tests. Thijssen et al. (2020) have found that a higher plasma p-tau181 level is correlated with a faster cognitive decline over 2.5 years. Further, they found that people with the highest levels are likely to develop Alzheimer’s over a period of up to 8 years [7]. Cullen et al. (2020) has demonstrated that p-tau181 did the best in predicting Alzheimer’s progression over 4 years, in comparison to other tau and amyloid proteins [8]. However, there is no tau blood test on the market.
If the C2N Diagnostics blood test becomes more affordable, substantiated with data, and suggested by physicians, it is definitely a viable option. It is expected that tau blood tests will soon be on the market as well, which would allow competition to lower the price and, hopefully, create more accessible and accurate blood tests. It is exciting to see rapid progression towards blood tests that allow patients to take more preventative measures. This test may encourage the development of blood tests for analysis of other neurodegenerative diseases.
References:
1. United Kingdom National Health Services. (2018). Causes: Alzheimer’s disease. Nhs.Uk. https://www.nhs.uk/conditions/alzheimersdisease/causes/#:%7E:text=Alzheimer’s%20disease%20is%20thought%2 0to,form%20tangles%20within%20brain%20cells.
2. Götz, J. T. C. (2018, January 18). Why it’s so hard to treat dementia. CNN. https://edition.cnn.com/2018/01/18/health/dementiaalzheimers-drug-treatment-partner
3. Alzheimer’s Association International Conference. (2020, July 20). A Blood Test for Alzheimer’s? Markers for Tau Take Us a Step Closer | AAIC 2020 | Alzheimer’s Association. AAIC. https://www.alz.org/aaic/releases_2020/blood-biomarkers-tau.asp
4. West, T. (2020, October 29). Alzheimer’s Breakthrough: C₂N First to Offer a Widely Accessible Blood Test. C2N Diagnostics. https://www.c2ndiagnostics.com/press/press/2020/10/28/alzheimersbreakthrough-cn-first-to-offer-a-widely-accessible-blood-test
5. Williams, S. (2020, November 2). First Alzheimer’s Blood Test Rolled Out for Clinical Use in US. The Scientist Magazine. https://www.thescientist.com/news-opinion/first-alzheimers-blood-test-rolled-outfor-clinical-use-in-us-68117
6. CBS News. (2020, December 1). First Alzheimer’s blood test now on the market, without FDA approval. https://www.cbsnews.com/news/alzheimers-blood-test-on-marketfirst-no-fda-approval/
7. Thijssen, E. H., La Joie, R., Wolf, A., Strom, A., Wang, P., Iaccarino, L., Bourakova, V., Cobigo, Y., Heuer, H., Spina, S., VandeVrede, L., Chai, X., Proctor, N. K., Airey, D. C., Shcherbinin, S., Duggan Evans, C., Sims, J. R., Zetterberg, H., Blennow, K., . . .Boxer, A. L. (2020). Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration. Nature Medicine, 26(3), 387–397. https://doi.org/10.1038/s41591-020-0762-2
8. Cullen NC, Leuzy A, Palmqvist S, et al. Plasma amyloid, phosphorylated tau, and neurofilament light for individualized risk prediction in mild cognitive impairment (2020). medRxiv. doi: 10.1101/2020.07.21.20159129.