Blood tests may soon accurately detect Alzheimer’s disease
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Recent advances in blood tests suggest future tests may be able to detect Alzheimer’s disease, according to data presented at the Alzheimer’s Association International Conference 2020.
“There is an urgent need for simple, inexpensive, non-invasive and easily available diagnostic tools for Alzheimer’s disease,” Maria C. Carrillo, PhD, chief science officer of the Alzheimer’s Association, said in a press release. “New testing technologies could also support drug development in many ways. For example, [they may do so] by helping identify the right people for clinical trials, and by tracking the impact of therapies being tested. The possibility of early detection and being able to intervene with a treatment before significant damage to the brain from Alzheimer's disease would be game changing for individuals, families and our health care system.”
Research presented at the conference highlighted advances in blood tests for abnormal versions of the tau protein. One such advanced test may be able to detect brain alterations 20 years prior to the occurrence of dementia symptoms, according to researchers. Specifically, p-tau217 appeared the most relevant to Alzheimer’s and was the earliest to demonstrate measurable changes.
“While these new reports are encouraging, these are early results, and we do not yet know how long it will be until these tests are available for clinical use,” Carrillo added. “They need to be tested in long-term, large-scale studies, such as Alzheimer’s clinical trials. In addition, we need to continue research to refine and verify the tests that are the current state-of-the-art — including cerebrospinal fluid and [positron-emission tomography] (PET) imaging biomarkers.”
P-tau217 accurately detects Alzheimer’s disease
P-tau217 measured in blood appeared to have equivalent diagnostic precision as established diagnostic methods, according to a study by Sebastian Palmqvist, MD, PhD, of Lund University in Sweden, and colleagues.
“Accurate clinical diagnosis of Alzheimer’s disease requires either lumbar puncture and analysis of cerebrospinal fluid or PET scans,” Palmqvist told Healio Psychiatry. “These investigations are expensive, invasive and only available to a very small fraction of affected individuals. There is thus a great need for non-invasive and inexpensive diagnostic tools, such as a diagnostic blood test.”
The investigators evaluated three cohorts with more than 1,400 total cases, including a large clinic-based study from Sweden, a large kindred with genetically caused Alzheimer’s disease from Colombia and a cohort with neuropathological confirmation of Alzheimer’s disease from Arizona. They performed PET imaging for tau and amyloid pathology and analyzed other current experimental biomarkers in both cerebrospinal fluid and blood.
Results showed a diagnostic accuracy between 89% and 98% for blood p-tau217’s ability to distinguish Alzheimer’s disease from other neurodegenerative disorders. P-tau217 assessment had higher accuracy for Alzheimer’s disease compared with blood-based test for p-tau181, neurofilament light or amyloid beta 42/40 ratio, as well as MRI. Further, it performance was comparable to methods with much higher costs, including PET imaging and cerebrospinal fluid biomarkers.
Palmqvist and colleagues also reported that p-tau217 analyzed in blood collected during life was able to detect brain alteration measured in brain tissue analyzed after death. P-tau217 levels were increased approximately seven-fold among those with Alzheimer’s disease. Moreover, among individuals with a gene causing Alzheimer’s disease, the levels began increasing 20 years before onset of cognitive impairment
“Centers that previously did not have access to cerebrospinal fluid analysis or PET can improve their diagnostic accuracy for Alzheimer’s disease by taking a blood sample and analyzing p-tau217,” Palmqvist told Healio Psychiatry. “However, additional optimization of the analysis method and further validation is required before it can be used in clinical practice.”
P-tau and blood amyloid precisely detect brain tauopathy, amyloidosis
Suzanne Schindler, MD, PhD, of Washington University School of Medicine in St. Louis, Mo., and colleagues conducted a study to evaluate the performance of multiple amyloid and tau blood measures.
“We are working to develop and validate a blood test for Alzheimer’s disease that detects both early brain changes in cognitively normal individuals and corresponds to the risk of significant cognitive impairment,” Schindler told Healio Psychiatry.
The researchers used mass spectrometry to map the blood plasma tau protein and compare the results to cerebrospinal fluid and PET imaging measures.
Results showed p-tau217 was more closely associated with amyloid plaque build-up in the brain as measured by a PET scan compared with p-tau181.
“An accurate blood test for Alzheimer’s disease is likely to be much more useful in clinical settings than amyloid PET scans or cerebrospinal fluid biomarkers, which are limited by cost, availability and perceived invasiveness,” Schindler told Healio Psychiatry. “These data demonstrate that plasma Ab42/Ab40, p-tau217 and p-tau181 provide similar information compared with amyloid PET and cerebrospinal fluid biomarkers of Alzheimer’s disease.”
Plasma p-tau217, p-tau181 comparably distinguish between Alzheimer’s disease and frontotemporal lobar degeneration
Results of prior studies suggested that those with Alzheimer’s disease have p-tau181 levels three times higher compared with healthy people of older age or people with the neurodegenerative disease frontotemporal lobar degeneration (FTLD). In the current retrospective study, Elisabeth Thijssen, MSc, of the University of California, San Francisco Memory and Aging Center, and colleagues reported outcomes of p-tau181 vs. p-tau217 for determining which form can best identify individuals with Alzheimer’s disease. The researchers analyzed data of 119 healthy controls, 75 biomarker-confirmed Alzheimer’s cases and 294 FTLD cases.
Results showed plasma p-tau181 was three times higher among individuals with Alzheimer’s disease compared with controls and FTLD; however, plasma p-tau217 was five times higher among those with Alzheimer’s disease vs. health controls and four times higher vs those with FTLD. These results mirrored the findings of tau PET brain imaging. Accuracy for predicting whether an individual had a tau-positive brain scan was 91% for p-tau181 and 96% for p-tau217.