Emerging Tests

Studies Show Blood Testing May Be Just as Good If Not Better than PET Scans in Detecting Early Alzheimer’s Disease

For decades, researchers have worked to create a cost-effective and accurate blood test for early detection of Alzheimer’s disease. A new study 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 offers new hopes of achieving that goal.

The Diagnostic Challenge

Alzheimer’s damages brain cells well before it impairs cognitive ability. And by the time patients manifest symptoms of impaired thinking, it is too late to treat them. That makes it critical to identify Alzheimer’s as early as possible before patients suffer cognitive impairment.

Alzheimer’s patients generate abnormally large amounts of certain proteins in the brain that clump together to form plaques, strangling nerves and severing nerve connections. Current diagnosis of Alzheimer’s relies largely on the use of positron emission tomography (PET) scans to 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 detection test—like a blood test.

The AAIC Study

One potential biomarker for early Alzheimer’s is an elevated level of the p-tau-217 protein. A study discussed at the annual Alzheimer’s Association International Conference (AAIC) in July and reported online in JAMA Neurology in November found 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 as this early stage.

The data reported in the JAMA Neurology piece derive from a cohort of a Swedish, which is partly supported by Eli Lilly, finding plasma p-tau-217 effective for discriminating Alzheimer’s from other neurodegenerative conditions, with better performance than p-tau-181, neurofilament light chain, and other biomarkers.

The Washington University at St. Louis Study

In another study reported at the AAIC, researchers at Washington University of 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, which were published in the Journal of Experimental Medicine on July 28, show 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.

Takeaway

Evidence continues to emerge that blood testing patients for elevated levels of different proteins is a viable method of detecting the onset of early Alzheimer’s disease, especially vis à vis PET scans. Blood tests that can be performed in a physician’s office or other point of care settings are not just more affordable and accessible than PET scans but they may actually be more reliable. Even so, the development and regulatory approval of such tests remains years away.

 


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