A new diagnostic protocol developed by researchers from Washington University School of Medicine involving blood analysis for the determination of levels of protein amyloid beta coupled with blood detection for the presence of the genetic variant APOE4,is able to identify with an accuracy of more than 94%, that an individual is predisposed to having early Alzheimer.
It normally takes anything between 15 to 20 years for the actual physical symptoms of Alzheimer to materialize such as characteristic memory loss and confusion due to the gradual build up and amyloid beta in the brain and the development of the signature clumps that distort normal cognitive functions of the brain.
This new diagnostic blood tests can help identify people on track to develop Alzheimer's before symptoms arise. The test may be even more sensitive than the platinum standard, a PET brain scan,
at detecting the beginnings of amyloid deposition in the brain.
Such a diagnostic test may become available at physicians' offices within a few months, but its benefits will be much greater once there are new pharmaceutical drugs to stop the disease process and forestall dementia. Clinical trials of preventive pharma drugs have been hampered by the difficulty of identifying participants who have Alzheimer's brain changes but no cognitive issues. The blood test could provide a way to efficiently screen for people with early signs of disease so they can participate in clinical trials evaluating whether trial drugs can effectively prevent Alzheimer's dementia.
The test uses a technique called mass spectrometry to precisely measure the amounts of two forms of amyloid beta in the blood: amyloid beta 42 and amyloid beta 40. The ratio of the two forms goes down as the amount of amyloid beta deposits in the brain goes up.
The study involved 158 adults over age 50. All but 10 of the participants in the study were cognitively normal, and each provided at least one blood sample and underwent one PET brain scan. The researchers classified each blood sample and PET scan as amyloid positive or negative, and found that the blood test from each participant agreed with his or her PET scan 88 percent of the time, which is promising but not accurate enough for a clinical diagnostic test.
In order to improve the test's accuracy, the team incorporated several major risk factors for Alzheimer's. Age is the largest known risk factor; after age 65, the chance of developing the disease doubles every five years. A genetic variant called APOE4 raises the risk of developing Alzheimer's three- to fivefold. And gender also plays a role: Two out of three Alzheimer's patients are females.
When the researchers included these risk factors in the analysis, they found that age and APOE4 status raised the accuracy of the blood test to 94%. Gender did not significantly affected the analysis.
There is growing consensus among specialists that Alzheimer's treatment needs to begin as early as possible, ideally before any cognitive symptoms arise. By the time people become forgetful, their brains are so severely damaged that it is beyond repair. But testing preventive treatments requires screening thousands of healthy people to find a study population of people with amyloid build-up and no cognitive problems, a slow and expensive process.
As part of the study,
the researchers analyzed the enrollment process for a prominent Alzheimer's prevention trial called the A4 study that used PET scans to confirm the presence of early Alzheimer's brain changes in potential participants. They concluded that prescreening with a blood test followed by a PET scan for confirmation would have reduced the number of PET scans needed by two thirds. Unlike blood tests, which cost less than US$200, each PET scan costs upward of US$4,000. A single site can only run a few dozen PET brain scans a month, because PET scanners are primarily reserved for patient care, not research studies. Using the new blood tests would help screen for candidates for a drug trial faster and also help to find a cure for Alzheimer faster.
Reference: Schindler SE, Bollinger JG, Ovod V, Mawuenyega KG, Li Y, Gordon BA, Holtzman DM, Morris JC, Benzinger TLS, Xiong C, Fagan AM, Bateman RJ. High precision plasma amyloid-β 42/40 predicts current and future brain amyloidosis. Neurology, August 1, 2019 DOI: 10.1212/WNL.0000000000008081