Predicting Alzheimer's Disease via Detection of Misfolded Amyloid-β in a Blood Sample

The research community is making progress towards forms of low cost testing for Alzheimer's disease risk. At present, the well established tests are invasive or expensive. The very early stages of Alzheimer's disease, in which symptoms are mild or absent, are characterized by increasing levels of amyloid-β in the brain. However, amyloid-β in the brain is in a state of dynamic equilibrium with amyloid-β in the bloodstream, and in principle a suitable sensitive test can use a blood sample to assess the relevant aspects of amyloid-β burden. It takes years to validate predictions of Alzheimer's risk of course, and here researchers report on a lengthy but successful validation of one particular blood sample assay.

Using a blood test, a research team has predicted the risk of Alzheimer's disease in people who were clinically diagnosed as not having Alzheimer's disease but who perceived themselves as cognitively impaired. The cohort included 203 individuals. Using a test called the Immuno-Infrared Sensor, they identified all 22 subjects at study entry who developed Alzheimer's dementia, thus the clinical symptoms, within six years.

At study entry, blood samples were taken from all the participants and analyzed using the patented immuno-infrared sensor that detects misfolding of the amyloid-beta (Aβ) peptide, which is a biomarker for Alzheimer's disease. In addition, the subjects underwent extensive Alzheimer's disease diagnostic testing; at study entry, this did not provide a diagnosis of Alzheimer's disease in any of the subjects studied. The immuno-infrared sensor, on the other hand, detected misfolded Aβ peptides at study entry in all 22 subjects who developed the clinical disease in the following six years. In subjects who showed mild misfolding, it took on average longer (3.4 years) for conversion to clinical Alzheimer than in subjects with severe Aβ misfolding (2.2 years).

In addition, the team checked whether the combination of two different measurement methods in the plasma biomarker panel could further improve the prediction of disease risk. For this purpose, they combined the misfolding of all Aβ isoforms with a concentration decrease for Aβ42 as ratio to Aβ40 in plasma. This increased the assay accuracy. Such a blood test, which can detect the onset of Alzheimer's dementia even in the asymptomatic state, would be particularly useful if a drug were available to treat the disease.


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