Blood Tests for Alzheimer's Disease Continue to Look Promising
In recent years, data has shown correlations between specific blood biomarkers and Alzheimer's disease pathology in the brain, such as the burden of misfolded, aggregated amyloid-β. This has led to the development of a variety of blood tests for Alzheimer's disease, intended to replace the presently onerous testing that requires either expensive imaging or invasive analysis of cerebrospinal fluid. Alzheimer's disease develops slowly over time, a long period of raised amyloid-β levels in the brain setting the stage for later dysfunction. Early testing for the risk of later Alzheimer's disease enabled attempts to slow or evade the condition, such as via lifestyle changes, use of antiviral therapies, or at worst undergoing immunotherapies to reduce the burden of amyloid-β in the brain.
Accurate and expeditious detection of Alzheimer's disease (AD) pathology continues to be a major hurdle in advancing AD-modifying clinical research. A robust screening process that can identify patients with a high probability to randomize into AD therapeutic research trials would greatly enhance the ability to conduct and reduce the time needed to complete clinical trials. AD is characterized by the accumulation of two protein aggregates in the brain: extracellular deposits of amyloid beta (Aβ)-containing plaques and intraneuronal aggregates of misfolded tau protein. Numerous AD clinical trials, particularly those targeting either Aβ or amyloid plaques have used amyloid PET scans and/or cerebrospinal fluid (CSF) measures as an inclusion criterion for enrollment. While amyloid PET tracers have been shown to be very accurate in detecting brain amyloid deposits, these scans are costly and impose a significant patient burden.
Blood-based measures that are associated with the presence of brain amyloid plaques have recently been developed. Additionally, there is substantial interest in blood-based biomarkers reflecting two other critical aspects of AD pathology: tau tangles and neurodegeneration. Several clinical studies have been conducted evaluating the ability of various blood-based biomarkers to identify AD. These studies have identified Aβ40, Aβ42, the Aβ42/Aβ40 ratio (Aβ42/Aβ40), tau, and several species of phosphorylated tau (p-tau) as good candidates.
The primary objective of the Bio-Hermes Study was to evaluate the ability of several promising blood-based and digital biomarkers to reflect the presence of brain amyloid in participants enrolled at clinical trial sites using recruitment procedures similar to those used in AD therapeutic drug studies. Participants in the Bio-Hermes Study had clinical characteristics similar to those enrolled in clinical trials of disease-modifying treatments and, because multiple biomarkers were obtained, the predictive value of biomarkers alone or in combination can be evaluated. Results indicate that Aβ42/Aβ40 ratio, p-tau181, and p-tau217 are good predictors of brain amyloid positivity in this clinical trial-ready population.