The FDA approval of Aduhelm as the first disease-modifying treatment for Alzheimer’s disease underscores the urgent need for a non-invasive widely available low-cost blood test to facilitate a diagnosis in the early stages of the AD disease continuum when therapeutic intervention is most likely to deliver clinical benefit. Currently established biomarker-based approaches to diagnostic workup include positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) biomarkers for amyloid and phosphorylated tau, both of which are invasive, expensive, and may not be widely available or covered by health insurance.

In tandem with progress in Alzheimer’s therapeutics, there has been rapid progress on development of tests for blood-based biomarkers that have the potential to enable non-invasive alternatives to CSF and PET biomarker modalities for assessing amyloid and tau pathology status, as well as brain structural changes. This progress has been enabled in large part by technical advances in mass spectrometry and ultrasensitive immunoassay techniques. One technology in particular, single molecule array (Simoa), has paved the way for blood-based immunoassay detection of CNS-derived biomarkers that have high diagnostic potential.  

Simoa technology digitizes immunoassays and operates through the counting of single molecules. This unprecedented sensitivity enables the robust quantification of low abundance biomarkers, such as CNS derived proteins in blood. Simoa technology is also multiplexible, allowing the combination of multiple assays into a single test, and the technology has been fully automated into a high throughput laboratory instrument (HDX). This Simoa platform is uniquely and ideally suited to reliably measure multiple blood-based protein biomarkers that have recently emerged with high diagnostic potential for Alzheimer's detection. This project proposes to combine the most promising plasma biomarkers (beta amyloid 1-40, beta amyloid 1-42, phosphorylated tau, neurofilament light chain, and glial acidic fibrillary protein) into an IVD test for early Alzheimer’s detection.

Additional details can be found in section B of the uploaded proposal document.