DKFZ: A newly developed blood test may indicate Alzheimer's disease on average eight years before the clinical diagnosis. This was demonstrated by scientists from the Ruhr University Bochum (RUB), the German Cancer Research Center (DKFZ) and the Saarland Cancer Registry with a large population-based cohort study from the Saarland. There is as yet no cure for Alzheimer's disease. It is often argued that progress in drug research has been hampered by the fact that the disease can only be diagnosed when it is too late for an effective intervention. Alzheimer's disease is thought to begin long before patients show typical symptoms like memory loss. Scientists have now developed a blood test for Alzheimer's disease and found that it can detect early indicators of the disease long before the first symptoms appear in patients. The blood test would thus offer an opportunity to identify those at risk and may thereby open the door to new avenues in drug discovery.
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 colleagues at the 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 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. 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 by PET imaging.
In a next step, the scientists investigated if their assay was able
to detect blood changes well ahead of disease onset. They used data from
ESTHER, a cohort study in Saarland Germany, led by Hermann Brenner
(DKFZ) and conducted in collaboration with the Saarland Cancer Registry.
The researchers compared blood samples of 65 participants that were
later 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
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.
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.: Amyloid blood
biomarker detects Alzheimer's disease.
EMBO Molecular Medicine, 2018, DOI: 10.15252/emmm.201708763