Developing a high-performance biomarker panel for Alzheimer’s Disease screening and staging
A simple search of the term ‘scourge of Alzheimer’s Disease’ (AD) brings up over half a million website hits. Around 15% of the population between the age of 67 to 74, and 44% of those 75 to 84 will develop AD.
The first biomarkers for AD (amyloid-beta deposits, neurofibrillary tangles, and neurodegeneration markers called ATN) were measured from cerebrospinal fluid, which is hard to sample and is an obvious barrier to wider population screening.
Recent blood-based markers for Alzheimer’s Disease
While blood-based biomarkers for the disease have been identified (p-tau181, p-tau217, and neurofilament light peptide, NfL), these proteins do not offer enough differentiation between the different stages of AD using existing methods of diagnosis.
A study by Liang and colleagues used a set of Olink Target 96 protein biomarker panels to examine 106 AD-affected plasma samples along with 74 healthy matched controls, measuring the blood plasma levels of 1160 proteins.
The foundation of a “high-performance blood-based test for clinical AD screening and staging”
Overall, 429 proteins were dysregulated in AD patients and 19 “hub” proteins representative of the AD plasma profile were selected to develop a model for AD classification.
This 19-marker panel was then validated against an independent cohort of 97 more samples (36 affected and 61 healthy controls), and sensitivity and specificity were measured to generate a receiver-operator characteristic (ROC) curve. The 19-protein model discriminated AD vs controls with an area under the curve (AUC) of 0.9690, substantially improving on the previously used ATN marker (AUC=0.9971).
The value of screening and long-term monitoring
The authors highlighted that their findings replicated known AD-associated plasma proteins but ‘also reveal hundreds of novel proteins that are altered in the blood in AD.’ Significantly, they were able to classify and stage disease by examining just 19 proteins, making this a potentially viable clinical approach. The 19 “hub” proteins were associated in distinct protein clusters, each associated with a different biological pathway, providing new insights into the underlying disease biology.
Taking this non-invasive biomarker approach also opens up the possibility to identify novel targets for future drug development in the fight against AD.
Citation
Jiang et al. (2021) Alzheimers & Dementia, DOI: 10.1002/alz.12369