Alzheimer’s disease (AD) is a progressive neurodegenerative dementia, impacting millions globally. A defining characteristic of AD is the loss of synaptic connections between neurons, a process closely associated with cognitive impairment. Biomarkers for evaluating synaptic integrity and forecasting cognitive outcomes are limited. Our research published in Nature Medicine (Oh, et. al., 2025) has identified a novel biomarker, the ratio of two cerebrospinal fluid (CSF) proteins, YWHAG and NPTX2, that reliably predicts cognitive decline in early AD, including in presymptomatic stages.

Current techniques for measuring this ratio, such as advanced proteomics, are costly and impractical for widespread clinical application. To overcome this barrier, we propose to develop cost-effective, scalable sandwich ELISA assays for CSF YWHAG:NPTX2. We will develop new custom monoclonal antibodies for YWHAG and NPTX2, optimize the ELISA assay, and validate it across independent AD cohorts including the Stanford Alzheimer’s Disease Research Center (ADRC) and Alzheimer’s Disease Neuroimaging Initiative (ADNI). Our objective is to deliver a dependable prognostic tool that enables prediction of cognitive trajectories in early AD, thereby enhancing patient care and clinical trial design.

The public health implications are substantial: an accessible assay could enable earlier identification of at-risk individuals, inform personalized treatment strategies, and enhance the efficiency of clinical trials by refining patient stratification. Collaborating with leading experts and industry partners, such as Biosynth, and ensuring the assay is freely licensable, we aim to expedite its clinical adoption. This innovative approach promises to transform AD prognosis and management, delivering significant benefits to patients, caregivers, and the broader healthcare community.