Amyloid Beta Blood Test Detects Asymptomatic Alzheimer’s Disease

An assay has been developed that determines the ratio of amyloid beta peptides in the blood and correlates with the accumulation of these Alzheimer’s disease risk factors in the brain.

Amyloid beta (Abeta) denotes peptides of 36–43 amino acids that are crucially involved in Alzheimer's disease as the main component of the amyloid plaques found in the brains of Alzheimer patients. The peptides derive from the amyloid precursor protein (APP), which is cleaved by the enzymes beta secretase and gamma secretase to yield Abeta. Researchers have been trying to develop a blood test to measure the level of Abeta peptides in order to identify individuals at risk for Alzheimer's disease before symptoms arise.

Toward this end, investigators at Washington University School of Medicine (St. Louis, MO, USA) examined whether the ratio of plasma Abeta 42/Abeta40, as measured by a recently developed high-precision assay, accurately diagnosed brain amyloidosis using amyloid PET or CSF p-tau181/Abeta42 as reference standards.

For this study, the investigators used an immunoprecipitation and liquid chromatography–mass spectrometry assay, which had been under development for the past couple of years. They measured Abeta42/Abeta40 in plasma and CSF samples from 158 mostly cognitively normal individuals that were collected within 18 months of an amyloid PET scan.

Results revealed that plasma Abeta42/Abeta40 had a high correspondence with amyloid PET status and CSF p-tau181/Abeta42. Combining the plasma Abeta42/Abeta40 ratio with age and APOE4 status yielded very high correspondence with amyloid PET. Individuals with a negative amyloid PET scan at baseline and a positive plasma Abeta42/Abeta40 had a 15-fold greater risk of conversion to amyloid PET-positive compared to individuals with a negative plasma Abeta42/Abeta40. Therefore, plasma Abeta42/Abeta40 could be used in prevention trials to screen for individuals likely to be amyloid PET-positive and at risk for Alzheimer disease dementia.

"Right now we screen people for clinical trials with brain scans, which is time-consuming and expensive, and enrolling participants takes years," said senior author Dr. Randall J. Bateman, professor of neurology at Washington University School of Medicine. "But with a blood test, we could potentially screen thousands of people a month. That means we can more efficiently enroll participants in clinical trials, which will help us find treatments faster, and could have an enormous impact on the cost of the disease as well as the human suffering that goes with it. Reducing the number of PET scans could enable us to conduct twice as many clinical trials for the same amount of time and money. It is not the $4,000 per PET scan that we are worried about. It is the millions of patients that are suffering while we do not have a treatment. If we can run these trials faster, that will get us closer to ending this disease."

The paper was published in the August 1, 2019, online edition of the journal Neurology.

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