Summary: A new blood test to detect biomarkers for Alzheimer’s disease is set to undergo trials in the Fall. The test will be able to identify traces of amyloid beta in blood samples with a high degree of accuracy.
Source: Lund University
Researchers from Lund University, together with the Roche pharmaceutical company, have used a method to develop a new blood marker capable of detecting whether or not a person has Alzheimer’s disease. If the method is approved for clinical use, the researchers hope eventually to see it used as a diagnostic tool in primary healthcare. This autumn, they will start a trial in primary healthcare to test the technique.
Currently, major support in the diagnostics of Alzheimer’s disease is the identification of abnormal accumulation of the substance beta-amyloid, which can be detected either in a spinal fluid sample or through brain imaging using a PET scanner.
“These are expensive methods that are only available in specialist healthcare. In research, we have therefore long been searching for simpler diagnostic tools”, says Sebastian Palmqvist, associate professor at the unit for clinical memory research at Lund University, a physician at Skåne University Hospital and lead author of the study.
In this study, which is a collaboration between several medical centres, the researchers investigated whether a simple blood test could identify people in whom beta-amyloid has started to accumulate in the brain, i.e. people with underlying Alzheimer’s disease. Using a simple and precise method that the researchers think is suitable for clinical diagnostics and screening in primary healthcare, the researchers were able to identify beta-amyloid in the blood with a high degree of accuracy.
“Previous studies on methods using blood tests did not show particularly good results; it was only possible to see small differences between Alzheimer’s patients and healthy elderly people. Only a year or so ago, researchers found methods using blood sample analysis that showed greater accuracy in detecting the presence of Alzheimer’s disease. The difficulty so far is that they currently require advanced technology and are not available for use in today’s clinical procedures”, says Sebastian Palmqvist.
The results are published in JAMA Neurology and based on studies of blood analyses collected from 842 people in Sweden (The Swedish BioFINDER study) and 237 people in Germany. The participants in the study are Alzheimer’s patients with dementia, healthy elderly people and people with mild cognitive impairment.
The method studied by the researchers was developed by Roche and is a fully automated technique which measures beta-amyloid in the blood, with high accuracy in identifying the protein accumulation.
“We have collaborated with Roche for a long time and it is only now that we are starting to approach a level of accuracy that is usable in routine clinical care around the world”, says Oskar Hansson, professor of neurology and head of the unit for clinical memory research at Lund University.
The researchers believe that this new blood sample analysis could be an important complement for screening individuals for inclusion in clinical drug trials against Alzheimer’s disease or to improve the diagnostics in primary care which will allow more people to get the currently available symptomatic treatment against Alzheimer’s disease.
“The next step to confirm this simple method to reveal beta-amyloid through blood sample analysis is to test it in a larger population where the presence of underlying Alzheimer’s is lower. We also need to test the technique in clinical settings, which we will do fairly soon in a major primary care study in Sweden. We hope that this will validate our results”, concludes Sebastian Palmqvist.
Source:
Lund University
Media Contacts:
Sebastian Palmqvist – Lund University
Image Source:
The image is in the public domain.
Original Research: Open access
“Performance of Fully Automated Plasma Assays as Screening Tests for Alzheimer Disease–Related β-Amyloid Status”. Sebastian Palmqvist, MD, PhD; Shorena Janelidze, PhD; Erik Stomrud, MD, PhD; Henrik Zetterberg, MD, PhD; Johann Karl, PhD; Katharina Zink; Tobias Bittner, PhD; Niklas Mattsson, MD, PhD; Udo Eichenlaub, PhD; Kaj Blennow, MD, PhD; Oskar Hansson, MD, PhD.
JAMA Neurology. doi:10.1001/jamaneurol.2019.1632
Abstract
Performance of Fully Automated Plasma Assays as Screening Tests for Alzheimer Disease–Related β-Amyloid Status
Importance
Accurate blood-based biomarkers for Alzheimer disease (AD) might improve the diagnostic accuracy in primary care, referrals to memory clinics, and screenings for AD trials.
Objective
To examine the accuracy of plasma β-amyloid (Aβ) and tau measured using fully automated assays together with other blood-based biomarkers to detect cerebral Aβ.
Design, Setting, and Participants
Two prospective, cross-sectional, multicenter studies. Study participants were consecutively enrolled between July 6, 2009, and February 11, 2015 (cohort 1), and between January 29, 2000, and October 11, 2006 (cohort 2). Data were analyzed in 2018. The first cohort comprised 842 participants (513 cognitively unimpaired [CU], 265 with mild cognitive impairment [MCI], and 64 with AD dementia) from the Swedish BioFINDER study. The validation cohort comprised 237 participants (34 CU, 109 MCI, and 94 AD dementia) from a German biomarker study.
Main Outcome and Measures
The cerebrospinal fluid (CSF) Aβ42/Aβ40 ratio was used as the reference standard for brain Aβ status. Plasma Aβ42, Aβ40 and tau were measured using Elecsys immunoassays (Roche Diagnostics) and examined as predictors of Aβ status in logistic regression models in cohort 1 and replicated in cohort 2. Plasma neurofilament light chain (NFL) and heavy chain (NFH) and APOE genotype were also examined in cohort 1.
Results
The mean (SD) age of the 842 participants in cohort 1 was 72 (5.6) years, with a range of 59 to 88 years, and 446 (52.5%) were female. For the 237 in cohort 2, mean (SD) age was 66 (10) years with a range of 23 to 85 years, and 120 (50.6%) were female. In cohort 1, plasma Aβ42 and Aβ40 predicted Aβ status with an area under the receiver operating characteristic curve (AUC) of 0.80 (95% CI, 0.77-0.83). When adding APOE, the AUC increased significantly to 0.85 (95% CI, 0.82-0.88). Slight improvements were seen when adding plasma tau (AUC, 0.86; 95% CI, 0.83-0.88) or tau and NFL (AUC, 0.87; 95% CI, 0.84-0.89) to Aβ42, Aβ40 and APOE. The results were similar in CU and cognitively impaired participants, and in younger and older participants. Applying the plasma Aβ42 and Aβ40 model from cohort 1 in cohort 2 resulted in slightly higher AUC (0.86; 95% CI, 0.81-0.91), but plasma tau did not contribute. Using plasma Aβ42, Aβ40, and APOE in an AD trial screening scenario reduced positron emission tomography costs up to 30% to 50% depending on cutoff.
Conclusions and Relevance
Plasma Aβ42 and Aβ40 measured using Elecsys immunoassays predict Aβ status in all stages of AD with similar accuracy in a validation cohort. Their accuracy can be further increased by analyzing APOE genotype. Potential future applications of these blood tests include prescreening of Aβ positivity in clinical AD trials to lower the costs and number of positron emission tomography scans or lumbar punctures.
