New blood test method may predict Alzheimer's disease

March 11, 2020

Alzheimer’s disease is an age-related brain disorder that develops over many years. Toxic changes in the brain slowly destroy memory and thinking skills. Symptoms most often first appear when people are in their mid-60s. The disorder gets worse over time and eventually leads to severe loss of mental function.

The process that destroys the brain involves two proteins called beta-amyloid and tau. Beta-amyloid clumps into plaques, which slowly build up between brain cells. Abnormal tau accumulates inside brain cells, forming tangles.

Researchers have found that PET scans of the brain and lab tests of spinal fluid can reveal disease-related changes, or pathology, twenty years before the onset of symptoms. Although the disorder is not reversable, early treatment may help preserve daily functioning for some time. Early diagnosis would also enable testing of novel drugs and other treatment approaches. However, PET imaging is expensive and involves radioactive agents, and spinal fluid tests are invasive, complex, and time-consuming. Researchers are looking for simpler, more cost-effective tests.

A team led by Dr. Adam Boxer at the University of California, San Francisco investigated whether a new blood testing technique called Simoa could be used to measure the concentrations of tau and predict development of Alzheimer’s disease. The study was funded in part by NIH's National Institute on Aging (NIA), National Institute of Neurological Disorders and Stroke (NINDS), and National Center for Advancing Translational Sciences (NCATS). Results were published in Nature Medicine.

The team collected blood samples from more than 400 people. They measured the concentration of ptau181—a modified version of tau that’s been linked with Alzheimer’s disease—in blood plasma, the liquid part of blood. Their analysis showed that the ptau181 in plasma differed between healthy participants and those with Alzheimer's pathology confirmed in autopsies. The test could also differentiate Alzheimer’s pathology from a group of rare neurodegenerative diseases known collectively as frontotemporal lobar degeneration.

The results with the plasma ptau181 test also mirrored results with two established biomarker tests for Alzheimer’s—a spinal fluid ptau181 test and a PET brain scan for beta-amyloid protein.

A research team in Sweden reported similar findings in a second paper published in the same journal issue. Using the same plasma ptau181 test, they were able to differentiate between Alzheimer's and other neurodegenerative diseases nearly as well as they could with a spinal fluid ptau181 test and a PET brain scan for tau protein. In addition, they followed participants for several years and observed that high levels of plasma ptau181 among those who were cognitively normal or had mild cognitive impairment could be used to predict later development of Alzheimer's dementia.

“The considerable time and resources required for screening research participants with PET scans and spinal taps slow the pace of enrollment for Alzheimer’s disease treatment studies,” says NIA Director Dr. Richard J. Hodes. “The development of a blood test would enable us to rapidly screen a much larger and more diverse group of volunteers who wish to enroll in studies.”

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