Blood test to detect Alzheimer’s years before the symptoms show moves closer to reality, reveals study
The test 'demonstrated remarkable promise' in discriminating between persons with and without Alzheimer’s disease, say researchers
In a breakthrough, a blood test that is highly accurate at detecting Alzheimer’s disease in people has been developed by researchers. The new blood test could distinguish Alzheimer’s from other neurodegenerative disorders with diagnostic accuracy between 89% and 98%. It could also identify signs of Alzheimer’s disease 20 years before memory and thinking problems start in people with a genetic mutation that causes the disease. “A new blood test demonstrated remarkable promise in discriminating between persons with and without Alzheimer’s disease, and in persons at known genetic risk may be able to detect the disease as early as 20 years before the onset of cognitive impairment,” says the research team in the analysis published in JAMA.
The research has the potential to make the diagnosis of Alzheimer’s a much simpler and more affordable process that can be widely available. The test, however, needs more validation in diverse populations and is not yet ready for wide use. Alzheimer’s is a debilitating and incurable disease that affects an estimated 5.8 million Americans, aged 65 years and older. Without the discovery of successful prevention therapies, the number of US cases is projected to reach nearly 14 million by 2050. The disease is characterized by the presence of plaques in the brain formed by a protein called amyloid-β, as well as aggregates of a protein, tau, that “form neurofibrillary tangles in the neurons” of Alzheimer's patients. Amyloid-β and tau start to change years before any cognitive symptoms, such as memory loss and confusion, become apparent.
Currently, the brain changes that occur before Alzheimer’s dementia symptoms appear can only be reliably assessed by positron-emission tomography (PET) scans and from measuring amyloid and tau proteins in the spinal fluid (CSF). These methods are expensive and invasive. Too often, they are unavailable because they are not covered by insurance or difficult to access, or both. Hence, for many years, researchers have tried to develop blood tests that could detect Alzheimer's disease before the onset of symptoms while being cheaper and less invasive than PET scans and spinal taps.
“An international team of researchers have identified a highly accurate, blood-based biomarker for the detection of Alzheimer’s disease by measuring levels of p-tau217 in blood, and validated the finding in multiple, diverse populations. The scientists found that the diagnostic precision of blood p-tau217 was as high as established diagnostic methods, including positron emission tomography (PET) imaging and cerebrospinal fluid biomarkers, which are invasive, costly, and less available,” says a statement from the Alzheimer’s Association international conference where the results were presented.
The team studied three different cohorts comprising more than 1,400 cases. Coordinated from Lund University in Sweden, it included 81 Arizona participants in Banner Sun Health Research Institute’s Brain Donation program who had clinical assessments and provided blood samples in their last years of life and then had neuropathological assessments after they died; 699 participants in the Swedish BioFINDER Study who had clinical, brain imaging, cerebrospinal fluid (CSF) and blood-based biomarker assessments; and 522 Colombian autosomal dominant Alzheimer’s disease (ADAD)-causing mutation carriers and non-carriers from the world’s largest ADAD cohort.
According to the analysis, measurements of phospho-tau217 (p-tau217), one of the tau proteins found in tangles, could provide a relatively sensitive and accurate indicator of both plaques and tangles — corresponding to the diagnosis of Alzheimer’s — in living people. “The p-tau217 blood test has great promise in the diagnosis, early detection, and study of Alzheimer’s. While more work is needed to optimize the assay and test it in other people before it becomes available in the clinic, the blood test might become especially useful to improve the recognition, diagnosis, and care of people in the primary care setting,” explains senior author Dr Oskar Hansson, professor of clinical memory research at Lund University, Sweden, who spearheaded the international collaborative effort. “This test, once verified and confirmed, opens the possibility of early diagnosis of Alzheimer’s before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” adds Dr Hansson, who leads the Swedish BioFINDER Study.
Dr Eric Reiman, executive director of Banner Alzheimer’s Institute in Phoenix and a senior author of the study, says blood tests like p-tau217 have the potential to revolutionize Alzheimer’s research, treatment, prevention trials and clinical care. “While there’s more work to do, I anticipate that their impact in both the research and clinical setting will become readily apparent within the next two years,” adds Reiman.
Researchers evaluated the new p-tau217 blood test in 1,402 cognitively impaired and unimpaired research participants from Arizona, Sweden and Colombia. “In the Arizona (Banner Sun Health Research Institute) Brain Donation Cohort, the plasma p-tau217 assay discriminated between Arizona Brain donors with and without the subsequent neuropathological diagnosis of intermediate or high likelihood Alzheimer’s (that is, characterized by plaques, as well as tangles that have at least spread to temporal lobe memory areas or beyond) with 89% accuracy. It distinguished between those with and without a diagnosis of high likelihood Alzheimer’s with 98% accuracy; and higher p-tau217 measurements were correlated with higher brain tangle counts only in those persons who also had amyloid plaques,” the findings state.
In the Swedish BioFINDER Study, the assay discriminated between persons with the clinical diagnoses of Alzheimer’s and other neurodegenerative diseases with 96% accuracy, similar to tau PET scans and CSF biomarkers and better than several other blood tests and MRI measurements. It also distinguished between those with and without an abnormal tau PET scan with 93% accuracy. In the Colombia Cohort, the assay began to distinguish between mutation carriers and non-carriers 20 years before their estimated age at the onset of mild cognitive impairment. “In each of these analyses, p-tau217 (a major component of Alzheimer’s disease-related tau tangles) performed better than p-tau181 (another component of tau tangles and a blood test recently found to have promise in the diagnosis of Alzheimer’s) and several other studied blood tests,” says the team.
Yet another research group independently reported evidence for p-tau217 testing. Scientists at the University of California, San Francisco, found it helped distinguish people with Alzheimer’s from those with another neurological disease — frontotemporal lobar degeneration — with 96% accuracy in a study of 617 people. A third study, which was published in the Journal of Experimental Medicine, shows that levels of p-tau217 are elevated during the early stages of Alzheimer's disease and could lead to a simple blood test capable of diagnosing the neurodegenerative disorder years before any symptoms begin to appear.