Top of the News: Early Results Show Blood Test’s Effectiveness in Early Alzheimer’s Detection

Developing a cost-effective blood test capable of accurately detecting early Alzheimer’s disease that can be furnished at a doctor’s office has been a goal for decades. And now comes word that achieving the goal may be closer than we realized—perhaps only years away.

The Challenge

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

The key to detection is the amyloid protein associated with the disease. Alzheimer’s patients generate abnormally large amounts of the protein that clump together to form plaques in the brain, strangling nerves and severing nerve connections. Unfortunately, current amyloid identification techniques, including PET scans, are relatively expensive and only about 70% accurate. What’s needed is a more accurate, easier and less costly amyloid detection test—like a blood test.

The New Blood Test

Industry has been working on developing such a test. And the Aug. 1 issue of the journal Neurology reports that researchers at Washington University School of Medicine in St. Louis that they’ve developed a blood-based test that may just fill the bill.

The researchers used mass spectrometry as part of a study to measure blood levels of amyloid beta, a protein biomarker for Alzheimer’s. By combining blood amyloid levels with a patient’s age and the presence of the genetic variant APOE4, the researchers were able to identify pre-symptomatic people with early Alzheimer’s brain changes at an accuracy level of 94%.

Study Details

Using amyloid PET scans as the primary reference standard for amyloidosis (“because it is a well-established biomarker that is widely used in clinical trials”), the researchers used a mass spectrometry assay to measure the amounts of two forms of amyloid beta in blood—amyloid beta 42 and amyloid beta 40. They found that the ratio of the two forms decreases as the amount of amyloid beta deposits in the brain increases.

Of the 158 participants of age 50+, the researchers found all but 10 cognitively normal. They measured amyloid beta in 210 plasma samples and conducted a PET brain scan for each participant and then classified each blood sample and PET scan as amyloid positive or negative. The finding: The participant’s blood test matched his/her PET scan 88% of the time—impressive but not accurate enough for a useable test.

So, the researchers set out to boost accuracy by incorporating the other two major Alzheimer’s risk factors into the test—age and presence of the APOE4 genetic variant. They also considered gender to the extent that two of three Alzheimer’s patients are women.

Although gender didn’t have much of an impact, the researchers found that including age and APOE4 status raised the blood test’s accuracy to 94%.

What’s Next?

According to the researchers, a blood test may become available at doctors’ offices within a few years. “A blood-based biomarker would enable more rapid and inexpensive screening of potential participants, particularly for prevention trials, where rates of negative amyloid PET scans are about 70%,” the researchers wrote.

One of the remaining challenges for blood-based Alzheimer’s testing is setting the threshold for “normal” and “high” levels of amyloid in the blood. Complicating that determination is the fact that while the diagnosis of Alzheimer’s requires the presence of amyloid, some people who harbor amyloid plaques don’t develop the disease.

Takeaway: If and when a blood test for early Alzheimer’s does make it to market, it’s likely to improve not only detection but treatment and prevention of the disease by giving a boost to new drug development. Explanation: One of the biggest problems of conducting clinical trials for new Alzheimer’s drugs is identifying participants who have Alzheimer’s-related brain changes but not cognitive problems. But an accurate Alzheimer’s blood-based test would go a long way in overcoming that problem.