Home 5 Clinical Diagnostics Insider 5 Blood-Based Alzheimer’s Tests Have Officially Arrived

Blood-Based Alzheimer’s Tests Have Officially Arrived

by | May 27, 2022 | Clinical Diagnostics Insider, Diagnostic Testing and Emerging Technologies, Emerging Tests-dtet

Recent developments suggest that we are on the precipice of a new age offering expanded options for Alzheimer’s diagnosis.

For decades, researchers and laboratories have worked to develop a cost-effective and accurate blood test for early detection of Alzheimer’s disease. And now those efforts are coming to fruition. Recent developments suggest that we are on the precipice of a new age offering expanded options for Alzheimer’s diagnosis.  

The Diagnostic Challenge

More than six million people in the US, most of them above age 65, may have dementia caused by Alzheimer’s disease, according to Mayo Clinic and National Institutes of Health estimates. Alzheimer’s damages brain cells well before it impairs cognitive ability. By the time patients manifest symptoms of impaired thinking, it is often too late to treat them. That makes it critical to identify Alzheimer’s as early as possible before patients suffer cognitive impairment and while treatment options are still available.

The key to detection is the amyloid protein associated with the disease. Alzheimer’s patients generate abnormally large amounts of these proteins in the brain that clump together to form plaques. These buildups strangle nerves and sever nerve connections. Positron emission tomography (PET) scans detect buildups of these proteins. But PET scans are relatively expensive and only about 70 percent accurate. What is needed is a more accurate, easier, and less costly Alzheimer’s detection test—like a blood test that can be administered in a physician’s office.

Discovery of New Alzheimer’s Biomarkers

Recent studies suggesting that elevated levels of the protein tau phosphorylated at threonine 217 (p-tau-217) is an accurate biomarker for early onset of Alzheimer’s offer new hopes of achieving that goal. One notable example is the study published in JAMA Neurology in November 2020 finding that blood tests for detecting abnormal tau metabolism in the brain were able to detect pathology earlier than PET scans in patients with preclinical Alzheimer’s disease.

Tests for p-tau-217 were performed on 490 people, including healthy controls and those with subjective cognitive decline or mild cognitive impairment. Researchers compared the various methods of early Alzheimer’s detection for their effectiveness in detecting preclinical disease. They found that plasma p-tau-217 levels were elevated during the early preclinical stages of Alzheimer’s when PET scans were not yet capable of detecting insoluble tau aggregates. In other words, blood tests were the only way to detect the critical p-tau-27 biomarker at this early stage.

In another study published in the Journal of Experimental Medicine, researchers at Washington University in St. Louis evaluated a mass spectrometry test for assessing p-tau-217 and other tau fragments using blood samples as small as 4 mL. The study included two cohorts—a discovery cohort with 36 participants and a validation cohort with 92 participants. The researchers paired nano liquid chromatography with tandem mass spectrometry for plasma testing. They also evaluated p-tau-217 levels in cerebrospinal fluid (CSF). 

The results showed that p-tau-217 (and p-tau-281) were both highly specific for amyloid pathology evident on PET scans in both cohorts. “Importantly, plasma and CSF p-tau-217 measures distinguished amyloid-positive, tau PET-negative participants from controls,” the researchers wrote.

The results suggest that plasma tau could be developed as a highly sensitive screening tool for individuals at risk of having amyloid pathology and a lower-cost alternative to PET imaging, the researchers concluded. Tau blood tests could also be complementary to beta-amyloid 42/40 ratio blood tests.

The First FDA Approval for an Alzheimer’s Blood Test

Tau-based blood tests for Alzheimer’s have been approved in the European Union and other countries and it was only a matter of time before an in vitro diagnostic for early detection of the amyloid plaques associated with Alzheimer's reached the US market. That time came on May 4, when the US Food and Drug Administration announced that it had granted de novo classification to Fujirebio Diagnostics’ Lumipulse G β-Amyloid Ratio (1-42/1-40) test for use on people 55 years and older with cognitive impairment who are being evaluated for Alzheimer's and other causes of cognitive decline.

The Lumipulse test detects the presence of amyloid plaques by measuring the ratio of β-amyloid 1-42 and β-amyloid 1-40 in patient CSF. In the clinical study supporting the de novo submission, researchers looked at a clinical study of 292 CSF samples from the Alzheimer’s Disease Neuroimaging Initiative sample bank and determined that 97 percent of individuals positive for plaques by the test were also positive by PET, while 84 percent of individuals who tested negative were also negative for amyloid on their PET scan.

According to the FDA, there is a risk of the Fujirebio assay’s generating false-positive and false-negative results, which could lead to psychological distress, delay in receiving a correct diagnosis, and expense and risk from unnecessary treatment. As a result, the agency has advised using the assay in conjunction with other tests.

A New Pipeline Opens

It is also significant to note that the FDA evaluated the Lumipulse test via its de novo premarket review pathway for novel technologies that are low to moderate risk. Under pathway rules, approval of a test creates a new regulatory pathway for other products of a similar type. To gain approval, test makers would have to demonstrate in their applications that their own products are substantially equivalent to the Lumipulse test.

“The availability of an in vitro diagnostic test that can potentially eliminate the need for time-consuming and expensive PET scans is great news for individuals and families concerned with the possibility of an Alzheimer’s disease diagnosis,” noted Jeff Shuren, director of the FDA’s Center for Devices and Radiological Health (CDRH), in a statement. “With the Lumipulse test, there is a new option that can typically be completed the same day and can give doctors the same information regarding brain amyloid status, without the radiation risk, to help determine if a patient’s cognitive impairment is due to Alzheimer’s disease.”

Bottom Line: Other test makers are likely to bring their own blood-based Alzheimer’s tests to the US market—and soon. For example, on May 4, the same day the FDA announced clearance for the Lumipulse test, Quest Diagnostics launched AD-Detect Amyloid Beta 42/40 Ratio for assessing a patient’s risk of Alzheimer's disease. Based on a CSF test that Quest developed in 2017, the assay evaluates amyloid beta peptides Aβ42 and Aβ40 and can be used to monitor changes over time to assess the potential risk of Alzheimer's disease progression. In addition to providing insights into the risk of Alzheimer's disease, AD-Detect may also help identify patients who are candidates for early antibody treatment, according to the company. Also keep in mind that blood-based prognostic tests predicting the future progress of Alzheimer’s disease are also making their way to the US market, including Diadem’s AlzoSure Predict test, which has already received Breakthrough Device designation from the FDA.

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