A new direct-to-consumer blood test for beta-amyloid – is it jumping the gun?

While doing a genetic genealogical search in 2012, I inadvertently discovered that I have two copies of the APOE-4 allele putting me at very high risk of developing Alzheimer’s dementia. However, as a neurologist, I knew that carrying the APOE-4 allele increases risk, but does not absolutely determine that one will get Alzheimer’s dementia.  Especially if there is one, not two copies of the APOE-4 alleles, then the increased risk is only about 2-fold. Other than advice on the website to seek advice from a genetic counselor, there was no support.  I did find a chat room for APOE-4 carriers, and perhaps not surprisingly, there was a dearth of information and a lot of panic. One person who had found that she had one copy of APOE-4 said she was considering suicide.  I responded to explain that there was a very good chance that she would never get Alzheimer’s dementia. Another person with a “positive” APOE-4 test revealed that he took another test at a dementia clinic and found that his original test was wrong. He did not carry any copies of the APOE-4 allele. I was surprised at the time that this sort of important genetic testing was being provided online with no apparent quality control or FDA authorization. Sure enough, in 2013 this company received a warning letter from the FDA to discontinue marketing its health-related genetic tests until it completed the agency’s regulatory review process. In 2017, FDA approval was finally granted for a direct-to-consumer test for late-onset Alzheimer’s disease risk (APOE-4).

Now the same thing appears to be happening again. A direct-to-consumer blood test for beta-amyloid is now being marketed by Quest Diagnostics. The test uses mass spectroscopy to measure the ratio of amyloid fragments Aβ42 and Aβ40 in blood plasma. The test does not have FDA approval, and there is no peer-reviewed data that experts can use to assess its value.  The only available data according to an article in Alzforum is a poster presentation given at the 2022 Alzheimer’s Association International Conference that claimed a sensitivity of 0.89, and a specificity of 0.71. The Alzheimer’s experts interviewed for the Alzforum article all agreed that this is not good enough for a direct-to-consumer test. “If it were used in a memory clinic population, where 60 percent of patients have amyloid plaques, it would misdiagnose 18 percent of them.” (Suzanne Schindler, MD, PhD at Washington University as quoted in Alzforum.)

Blood tests for amyloid and tau are getting really good, and they should be widely available soon. In my opinion, they will eventually be very important in identifying people with very early Alzheimer’s disease who might most benefit from treatment. They will largely replace the unpleasantness of a spinal tap and the expense of PET scans (except in research). For now and for the foreseeable future, the new blood tests will still need to be used in conjunction with a complete neurological exam, expert cognitive testing, and brain imaging to rule out mimics of Alzheimer’s disease.