- A blood test for the detection of Alzheimer's disease before the detection of symptoms has the potential to change the paradigm of treatment.
- Early detection can reduce the cost of Alzheimer's treatment by administering treatment before significant damage is done and delay the progression of the disease.
- Using a blood test as a screening method for clinical trials can improve acceptance, reduce costs, and increase the ability of the drug to progress through development.
As the trend for disease prevention and contraction continues to grow, a blood test to detect brain changes in early Alzheimer's disease is undergoing clinical development. Researchers at the University of Washington School of Medicine at St. Louis have reported that they can measure Alzheimer's beta amyloid beta protein levels in the blood and use such levels to predict whether protein has accumulated in the brain. The results are a key step towards a blood test to diagnose people who are on the road to developing a devastating disease before the onset of symptoms.
The study found that when blood amyloid levels are combined with two major Alzheimer's risk factors, age and the presence of the APOE4 genetic variant, people with early brain Alzheimer's can be identified with 94% accuracy. It has been noted that the test may be even more sensitive than the gold standard, PET scan of the brain, upon detection of the onset of amyloid deposition in the brain.
The test uses mass spectrometry to accurately 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 decreases as the amount of amyloid beta deposits in the brain increases. This study included 158 adults over the age of 50. All but 10 of the participants in the new study were cognitively normal and each provided at least one blood sample and underwent one PET examination of the brain. The researchers classified each blood sample and PET scan as positive or negative for amyloid and found that each participant's blood test agreed with his PET scan 88% of the time, which is promising but not accurate enough for a clinical diagnostic test.
In an attempt to improve the accuracy of the test, the researchers included several major risk factors for Alzheimer's disease. Age is the biggest known risk factor; after age 65, the chance of developing the disease doubles every five years. A genetic variant called APOE4 increases the risk of developing three to five times Alzheimer's, and gender also plays a role, with two out of three Alzheimer's patients being female. When researchers included these risk factors in the analysis, they found that the age and condition of APOE4 increased the accuracy of the blood test by up to 94%. Sex does not significantly affect analysis.
In addition, some people's blood test results are initially considered false positives, as the blood test is positive for amyloid beta, but the brain test returns negative. But some people with inconsistent results tested positive in follow-up brain tests, taken an average of four years later. The discovery suggests that the initial blood tests noted early signs of the disease, missed on the gold standard brain scan.
Alzheimer's disease is a growing burden that attracts device and pharmaceutical developers despite the high risk. According to the Alzheimer's Association, approximately 5.8 million Americans of all ages are living with Alzheimer's dementia in 2019. Due to the increasing number of people age 65 and older in the United States, the annual number of new Alzheimer's cases is expected to reach 14 million by 2050. Alzheimer's and other dementias are estimated to cost $ 277 billion, estimated at $ 1 trillion by 2050. Increasing prevalence and costs are leading to the search for innovative treatments and diagnostics.
Alzheimer's risk increases with age
Estimated risk of life for Alzheimer's dementia, by gender, aged 45 and 65 years
Source: Alzheimer's Association, Fitch Solutions
Early detection can transform Alzheimer's treatment. According to the study, up to two decades before people develop the characteristic memory loss and confusion of Alzheimer's disease, protein lumps are beginning to accumulate in their brains. There is a growing consensus among neurologists that Alzheimer's treatment should start as early as possible, ideally before any cognitive symptoms occur. By the time people become oblivious, their brains are so badly damaged, therapy is unlikely to cure them completely. But testing preventative treatments requires the screening of thousands of healthy people to find a studied population of people with amyloid accumulation and no cognitive problems, a slow and expensive process.
The Alzheimer's Association estimates that early diagnosis can save $ 7.9 trillion for the current US population. This is reflected in the increasing number of companies developing new diagnostics to improve the diagnosis of the disease. Currently, the diagnosis of Alzheimer's disease is largely based on clinical symptoms, including cognitive tests, with a significant number of patients being diagnosed when their disease is already advanced. Alzheimer's diagnosis based on cognitive measures is only correct in 70-80% of cases.
The screening test may have an impact on Alzheimer's clinical trials. Clinical trials of preventive drug candidates have been hampered by the difficulty of identifying participants who have Alzheimer's brain but are not aware of the problem. A blood test can provide a way for effective screening for people with early signs of the disease so that they can participate in clinical trials evaluating whether medications can prevent Alzheimer's dementia.
As part of the study, researchers analyzed the process of enrolling in an Alzheimer's prevention study called the A4 Study, which uses PET scans to confirm the presence of early Alzheimer's brain changes in potential participants. They concluded that pre-screening with a blood test, followed by a PET scan for confirmation, would reduce the number of PET scans required by two-thirds. Unlike blood tests, which cost several hundred dollars, each PET scan costs upwards of $ 4000. One site can only perform a few dozen PET brain scans per month, since PET scanners are reserved primarily for patient care rather than studies.