Scientists said Monday they had developed a way of predicting if patients will develop Alzheimer’s disease by analysing their blood, in what experts hailed as a potential “gamechanger” in the fight against the debilitating condition.
Around 50 million people live with Alzheimer’s, a degenerative brain disease that accounts for more than half of global dementia cases.
While its precise mechanism is not fully understood, Alzheimer’s appears to result from the accumulation of proteins in the brain that are thought to lead to the death of neurons.
Some of these proteins are traceable in the blood of patients and tests based on their concentrations can be used to diagnose the disease.
Scientists in Sweden and Britain now believe blood tests can be used to predict Alzheimer’s years before the onset of symptoms.
Writing in the journal Nature Aging, they described how they developed and validated models of individual risk based on the levels of two key proteins in blood samples taken from more than 550 patients with minor cognitive impairments.
The model based off of these two proteins had an 88 percent success rate in predicting the onset of Alzheimers in the same patients over the course of four years.
They said that while further research was needed, their prediction method could have significant impact on Alzheimer’s cases, given that “plasma biomarkers” from blood tests are “promising due to their high accessibility and low cost”.
Richard Oakley, head of research at the Alzheimer’s Society, said the main struggle in battling the disease was diagnosing cases early enough to intervene with experimental treatments.
“If these blood biomarkers can predict Alzheimer’s in larger, more diverse groups, we could see a revolution in how we test new dementia drugs,” he said.
Musaid Husain, professor of neurology at the University of Oxford, described Monday’s research as a “potential gamechanger.”
“For the first time, we have a blood test that can predict well the risk of subsequent development of Alzheimer’s disease in people who have mild cognitive symptoms,” said Husain, who was not involved in the study.
“We need further validation (of the results) but in the context of other recent findings this could be a transformative step to earlier diagnosis, as well as testing new treatments at earlier stages of the disease.”
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 online on March 2, 2020, 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.”
More information: Individualized prognosis of longitudinal cognitive decline and dementia in mild cognitive impairment based on plasma biomarker combinations, Nature Aging, DOI: 10.1038/s43587-020-00003-5 , www.nature.com/articles/s43587-020-00003-5
