New Alzheimer’s Blood Test Supports Early Diagnosis & Patient Selection

Alzheimers Disease

A blood test to diagnose Alzheimer’s disease launched in April by Quest Diagnostics has the potential to screen patients for risk years before symptoms appear. It can identify biomarkers in the blood even before the beta amyloid can be identified by positron emission tomography (PET) scans or before beta amyloid, tau and phosphor-tau can be detected by standard-of-care cerebrospinal fluid analysis.

“This could turn medicine on it head,” Michael Racke, M.D., medical director at Quest Advanced Neurology told BioSpace. “We’re using this test to identify people who are normal cognitively but are at risk for developing Alzheimer’s disease.

“Sensitivity and specificity for the test are in the range of 85 to 90%,” but including additional factors in the assessment, like the patient’s age and apolipoprotein E (APOE) condition, can improve accuracy. As Racke explained, “Having an APOE4 allele enhances your risk for developing Alzheimer’s disease, and this test measures that risk.

“The other important thing this test does is measure amyloid deposition occurring in the brain,” he continued. “People could be biomarker-positive in their 50s and 60s and still have normal cognitive function,” so this test can provide an early warning. That is important, Racke said, because by the time patients are symptomatic and have positive PET scans, the damage - in the form of lost neurons and synapses - is already done.

That’s a key reason people, according to the recent Quest survey, want to be tested at age 57 rather than the current average age of 66. They want interventions to be able to begin earlier.

False positives are rare. “But why would you get false positives?” Racke asked. “It’s because there are other disorders that also have beta amyloid and tau abnormalities, such as Parkinson’s disease, Lewy body dementia and frontotemporal dementia. So, when physicians look at clinical trials and research, they shouldn’t use just one biomarker to diagnose Alzheimer’s disease. Instead, use the ATN framework – amyloid, tau, neurodegeneration – so they can be very specific in the characterization,” and, therefore, in the choice of intervention.”

If the test results are negative, physicians know to look for other causes of their symptoms. Sometimes, Racke said, a simple vitamin B12 deficiency is behind Alzheimer’s-like symptoms. Likewise, “Patients with severe depression can become so inattentive that it would be difficult to determine clinically whether they had Alzheimer’s disease.”

For decades, the importance of diagnosing Alzheimer’s disease was downplayed because there were no therapies to halt disease progression or reverse its effects. Today, that’s changing. While aducanumab remains controversial, other therapies are in clinical trials. Some of those appear to have potential to even reverse some of the effects of Alzheimer’s. According to a survey of physicians conducted by Quest, “Two-thirds said we’re at the precipice of having breakthrough treatments for this disease.”

The availability of a simple blood test to diagnose Alzheimer’s disease also makes it easier to identify and recruit patients for clinical trials, according to 95% of survey respondents.  He advised, however, looking at biomarkers that are very specific for a particular therapy.

Currently, recruitment is challenging. As Racke recalled, “The Alzheimer’s Clinical Trial Consortium was looking at approximately 40,000 people who were interested in being evaluated, but only about 300 were able and willing to come into an Alzheimer’s disease research center.” Having a test performed at one of the 2,000 Quest Patient Service Centers in the U.S. (or others around the world), however, is easier for many patients simply because of proximity. “Then, if they are found to be at risk, they are more likely to make the trip to a major medical center.”

Quest is working with scientists to determine how much advance warning this blood test provides. It wants to know the likely time frame for biomarkers to be detected on a PET scan, the time frame for physical symptoms to manifest and which factors influence that. “It’s clear that APOE status is one of those factors, and age is another,” he said. “We’re involved with a number of big research projects that are looking at that.”

The company is also looking at more diverse communities. “Most of the studies that researchers have conducted looked at well-educated Caucasian patients. Now we’re very much involved in looking at what happens in more diverse patient subgroups,” Racke said. “For example, how do comorbidities such as hypertension, diabetes, heart disease, stroke, etc. affect the ability of the test to predict when a person will have cognitive dysfunction?”

In terms of rolling this out, he said, “In our survey, two-thirds of physicians said they wanted more education about the test, how it can be used with other tests and how it can identify patients for clinical trials.” Nearly 9 of 10 predicted this test would probably become standard of care.

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