One of the hallmarks of Alzheimer’s disease is the accumulation of amyloid-β plaques in the patient’s brain. The blood test, developed by Klaus Gerwert and his team at Ruhr University Bochum, Germany, works by measuring the relative amounts of a pathological and a healthy form of amyloid-β in the blood. The pathological form is a misfolded version of this molecule and known to initiate the formation of toxic plaques in the brain. Toxic amyloid-β molecules start accumulating in the patients’ body 15-20 years before disease onset. In the present study, Gerwert and colleagues from Germany and Sweden addressed whether the blood test would be able to pick up indications of pathological amyloid-β in very early phases of the disease.
The researchers first focused on patients in the early, so called prodromal stages of the disease from the Swedish BioFINDER cohort conducted by Oskar Hanson. They found that the test reliably detected amyloid-β alterations in the blood of participants with mild cognitive impairment that also showed abnormal amyloid deposits in brain scans.
In a next step, Gerwert and colleagues investigated if their assay was able to detect blood changes well ahead of disease onset. They used data from the ESTHER cohort study, which Hermann Brenner started in 2000 at DKFZ, comparing blood samples of 65 participants that were later in the follow-up studies diagnosed with Alzheimer’s disease with 809 controls. The assay was able to detect signs of the disease on average eight years before diagnosis in individuals without clinical symptoms. It correctly identified those with the disease in almost 70% of the cases, while about 9% of true negative subjects would wrongly be detected as positive. The overall diagnostic accuracy was 86%.
Currently available diagnostic tools for Alzheimer’s disease either involve expensive positron emission tomography (PET) brain scans, or analyze samples of cerebrospinal fluid that are extracted via lumbar puncture. The researchers suggest that their blood test serves as a cheap and simple option to pre-select individuals from the general population for further testing by these more invasive and costly methods to exclude the falsely positive subjects.
The blood test developed by Gerwert and colleagues uses a technology called immuno-infrared sensor to measure distribution of pathological and healthy structures of amyloid-β. The pathological amyloid-β structure is rich in a sticky, sheet-like folding pattern that makes it prone to aggregation, while the healthy structure is not. The two structures absorb infrared light at a different frequency, allowing the blood test to determine the ratio of healthy to pathological amyloid-β in the sample.
The blood test will be extended to Parkinson disease by measuring another disease biomarker – α-synuclein − instead of amyloid-β.
INFORMATION FOR EDITORS
Amyloid blood biomarker detects Alzheimer’s disease
Andreas Nabers, Laura Perna, Julia Lange, Ute Mons, Jonas Schartner, Jörn Güldenhaupt, Kai-Uwe Saum, Shorena Janelidze, Bernd Holleczek, Dan Rujescu, Oskar Hansson, Klaus Gerwert, Hermann Brenner
About EMBO Molecular Medicine and EMBO Press
EMBO Molecular Medicine is one of four leading journals published by EMBO Press. It is a peer-reviewed, online Open Access journal dedicated to a new research discipline at the interface between clinical research and basic biology. It offers those working in this area the opportunity to publish their best work in a broadly distributed and highly visible forum, thereby helping to forge new links between clinicians and molecular biologists.
EMBO Press stands for publishing impactful, high quality and reliable research across the biosciences in its four journals, The EMBO Journal, EMBO Reports, Molecular Systems Biology and EMBO Molecular Medicine.
EMBO Press pioneered the transparent editorial process in order to provide a rapid, fair and efficient publication process. Through developing and employing Source Data tools, EMBO Press works towards improving data transparency, reuse and discoverability. Through dedicated data integrity checks, it ensures the publication of reliable data. All submitted manuscripts are subject to scooping protection, which extends to manuscripts published on preprint servers. As a co-signatory of the San Francisco Declaration for Research Assessment, EMBO Press is an advocate for moving away from impact factors as a mechanism for research assessment.
EMBO is an organization of more than 1700 leading researchers that promotes excellence in the life sciences. The major goals of the organization are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information, and help build a European research environment where scientists can achieve their best work.
EMBO helps young scientists to advance their research, promote their international reputations and ensure their mobility. Courses, workshops, conferences and scientific journals disseminate the latest research and offer training in techniques to maintain high standards of excellence in research practice. EMBO helps to shape science and research policy by seeking input and feedback from our community and by following closely the trends in science in Europe.
For more information: www.embo.org