04/08/2020
At the Alzheimer’s Association International Conference ® (AAIC®) 2020, scientists reported results of multiple studies on advances in blood “tests” for abnormal versions of the tau protein, one of which may be able to detect changes in the brain 20 years before dementia symptoms occur. In particular, the reports focus on a specific form of tau known as p-tau217, which seems to be the most specific to Alzheimer’s and the earliest to show measurable changes.
Changes in brain proteins amyloid and tau, and their formation into clumps known as plaques and tangles, respectively, are defining physical features of Alzheimer’s disease in the brain. Buildup of tau tangles is thought to correlate closely with cognitive decline. In these newly reported results, blood/plasma levels of p-tau 217, one of the forms of tau found in tangles, also seem to correlate closely with buildup of amyloid.
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 spinal fluid (CSF). These methods are expensive and invasive. And, too often, they are unavailable because they are not covered by insurance or difficult to access, or both.
Blood P-tau217 Detects Alzheimer’s Disease (i.e., Both Plaques and Tangles) with High Accuracy
As reported at AAIC 2020, 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.”
They studied three different cohorts comprising more than 1,400 cases, including a large clinic-based study from Sweden (the BioFINDER-2 study), a cohort with neuropathological confirmation of Alzheimer’s (the Arizona Study of Aging and Neurodegenerative Disorders), and a large kindred with genetically-caused Alzheimer’s (Colombian autosomal-dominant Alzheimer’s registry).They analyzed other current experimental biomarkers (p-tau217, p-tau181, Aβ42/40 and neurofilament light chain) in both blood and cerebrospinal fluid, as well as performed PET imaging for tau and amyloid pathology.
The main finding of the study was that blood p-tau217 could distinguish Alzheimer’s from other neurodegenerative disorders with diagnostic accuracy between 89 and 98 percent. In this study, the p-tau271 assessment was more accurate for Alzheimer’s than blood-based tests for p-tau181, neurofilament light or amyloid beta 42/40 ratio, as well as magnetic resonance imaging (MRI). In fact, according to the researchers, performance was similar to significantly more costly methods, such as PET imaging and cerebrospinal fluid biomarkers.
The researchers also found that p-tau217 analyzed in blood collected during life could detect tau brain changes measured in brain tissue analyzed after death. These tau brain changes are thought to be related to amyloid plaque accumulation. P-tau217 distinguished persons who had plaques and tangles from those without Alzheimer’s pathology with 89% accuracy, those with plaques and more extensive tangles with 98% accuracy, and the outcome of tau PET imaging with 93% accuracy.
The p-tau217 levels were increased about seven-fold in Alzheimer’s, and, in individuals with a gene causing Alzheimer’s, the levels started to increase already 20 years before onset of cognitive impairment. “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,” said the principal researcher Oskar Hansson, M.D., Ph.D., from Lund University, Sweden.
Autor: Arantxa Perales