Development of "Imagnostix": A Liquid Biopsy System for Alzheimer's Disease

PROJECT SUMMARY Development of AD/ADRD may take 15 to 20 years prior to symptoms. However, current diagnosis and differentiation of AD/ADRD from other dementias and even cognitive decline associated with aging is mostly symptom-based, heavily relying on neurological and cognitive tests, followed by confirmation with biomarker- specific positron emission tomography (PET) imaging and most recently detection of changes in AD biomarkers in cerebrospinal fluid (CSF). Delayed diagnosis and lack of treatment options to slow or reverse disease progression are major challenges in managing AD/ADRD, largely due to the lack of early and accurate diagnostic. Detecting AD at prodromal or even pre-symptomatic stage to allow timely intervention has been considered the best approach to manage AD/ADRD. While recent FDA-approvals of two disease-modifying drugs, i.e., Aducanumab (accelerated approval in 2021) and Lecanemab (traditional approval in 2023), along with those in the pipeline, such as Donanemab for early symptomatic AD participants8, are significant advances that brought hope for many AD patients and their families. These treatments are only effective when patients can be diagnosed at an early stage and present the pathology targeted by these new drugs. Therefore, there is an urgent demand for biomarker-based detections for early diagnosis for AD/ADRD, stratification of patients for treatment and monitoring treatment responses and disease progression, in particular, cost-effective, easy-to- access and repeatable tests that can be routinely applied for patients and those with AD/ADRD risks. The urgent need of blood sample-based AD diagnosis promoted FDA’s recent breakthrough device designations for two blood-based AD detection systems, i.e., PrecivityAD® (2019) and SIMOA® (2022). Both detections require blood sample processing, storage and transportation, before measurement using highly sophisticated analytic instruments by highly-skilled and experience personnel, all of which can limit their availability and cost- effectiveness. This Phase II SBIR project aims to develop a multiplexed liquid biopsy, namely Imagnostix, for detection and quantification of four AD biomarkers. Imagnostix is anticipated to be cost-effective, deployable, easy to operate, and capable of quick turn-around test, while still offering a good detection sensitivity. It can be used for routine blood tests of individuals at risk, monitoring of disease progression or treatment responses, and in the future, even screening AD/ADRD.