Blood Test May Detect Very Early Alzheimer's

A new blood test may be capable of detecting early biological indicators of Alzheimer’s disease long before the first symptoms appear.

The research, from Ruhr University Bochum in Germany, is published in EMBO Molecular Medicine.

A major hallmark of Alzheimer’s disease is the accumulation of amyloid-beta plaques in the brain. The blood test works by measuring the relative amounts of both a pathological and a healthy form of amyloid-beta in the blood. The pathological form is a misfolded version of the molecule and is known to jump-start the development of toxic plaques in the brain.

These toxic amyloid-beta molecules begin accumulating in the patient’s body 15-20 years before disease onset. In the new research, Ruhr study leader Dr. Klaus Gerwert and colleagues from Germany and Sweden looked into whether the blood test would be able to pick up indications of pathological amyloid-beta in the very early stages of the disease.

The team first focused on patients in the early (prodromal) phase of the disease who were enrolled in the Swedish BioFINDER cohort. They discovered that the test successfully detected amyloid-beta alterations in the blood of participants with mild cognitive impairment and who also showed abnormal amyloid deposits in brain scans.

Next, the researchers investigated whether their assay was able to detect blood changes well ahead of disease onset. Using data from the ESTHER cohort study, they compared the blood samples of 65 participants who would be diagnosed with Alzheimer’s disease at a later time with 809 controls.

With an overall accuracy of 8 percent, the researchers were able to detect signs of Alzheimer’s in individuals without clinical symptoms on average eight years before diagnosis. The test correctly identified those with the disease in almost 70 percent of the cases, while about 9 percent of true negative subjects would wrongly be detected as positive.

The current diagnostic tools for Alzheimer’s disease either involve expensive positron emission tomography (PET) brain scans, or analyze samples of cerebrospinal fluid taken via lumbar puncture. The researchers suggest their blood test offers an inexpensive and simple option to help identify individuals from the general population who would be candidates for further testing.

The blood test uses a technology called immuno-infrared sensor to measure the distribution of pathological and healthy structures of amyloid-beta. The pathological amyloid-beta structure is rich in a sticky, sheet-like folding pattern that makes it prone to clustering, while the healthy structure is not. The two structures absorb infrared light at a different frequency, allowing the test to pinpoint the ratio of healthy to pathological amyloid-beta in the sample.

The blood test will be extended to Parkinson disease by measuring another disease biomarker, alpha-synuclein, rather than amyloid-beta.

Source: EMBO