Blood circulating biomarkers that can predict the levels of amyloid beta plaque deposit in the brain have been reported in the scientific journal Nature.

The findings demonstrate potential clinical use of these plasma biomarkers in predicting brain amyloid-beta status in an individual - the earliest pathological signature of Alzheimer’s disease (AD).

Background

Alzheimer’s disease pathogenesis is believed to be driven by the production and deposition of the amyloid beta peptide. One of the hallmark pathologies required for a diagnosis of AD is the extracellular plaque deposit of the β-amyloid peptide (Aβ).

Currently, the levels of β-amyloid peptide in the brain can only be assessed reliably with PET imaging (positron-emission tomography), or by measuring their levels in the cerebrospinal fluid. A more cost-effective and less-invasive diagnostic tool is, therefore, urgently needed.

The research and results

Using an approach that combines a technique known as immunoprecipitation with mass spectrometry, the team of researchers from Japan and Australia measured the levels of several amyloid-beta-associated peptide fragments in the blood.

They tested their method using two independent datasets — a discovery dataset from Japan with samples from 121 people, and a validation dataset from Australia comprising 252 samples. Both cohorts included cognitively normal individuals, individuals with mild cognitive impairment and patients with Alzheimer’s disease.

They show that ratios of the different amyloid-beta-associated peptide fragments and a composite score can predict the level of amyloid-beta deposition in an individual’s brain.

According to the researchers, accuracy of the test biomarkers is approximately equal to 90% when matched with diagnosis with PET imaging, and they are correlated with amyloid beta PET burden and levels of amyloid beta peptide in cerebrospinal fluid.

Implications

The researchers suggest that these plasma biomarkers are minimally invasive, have cost–benefit and scalability advantages over current techniques, and can potentially provide broader clinical use such as at-risk population screening.

However, the researchers also note that the application and usefulness of these biomarkers as a monitoring tool for brain amyloid beta status remains to be further evaluated and validated.