Amyloid Blood Biomarker Detects 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.

Scientists at Ruhr University Bochum (Bochum, Germany) measured the relative amounts of a pathological and a healthy form of amyloid-beta (Aβ) in the blood. The blood test developed uses a technology called immuno-infrared sensor to measure distribution of pathological and healthy structures of Aβ. The team developed an immuno‐infrared‐sensor that monitored the secondary structure change of Aβ peptides. The sensor is an antibody‐based (immuno) method to extract all Aβ peptides from CSF and blood samples and spectroscopically senses the secondary structure distribution of extracted soluble Aβ peptides in the infrared. The two structures absorb infrared light at a different frequency, allowing the blood test to determine the ratio of healthy to pathological amyloid-beta in the sample.

The pathological form is a misfolded version of this molecule and known to initiate the formation of toxic plaques in the brain. Toxic Aβ molecules start accumulating in the patients' body 15-20 years before disease onset. They have recently addressed whether the blood test would be able to pick up indications of pathological Aβ in very early phases of the disease.

They 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 Aβ alterations in the blood of participants with mild cognitive impairment that also showed abnormal amyloid deposits in brain scans. They then compared 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%.

The authors 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 will be extended to Parkinson disease by measuring another disease biomarker - alpha-synuclein - instead of amyloid-beta. The study was published on March 4, 2018, in the journal EMBO Molecular Medicine.

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Ruhr University Bochum