Target-ad: a precision medicine framework for alzheimer's disease

The National Institute on Aging, part of the Department of Health and Human Services National Institutes of Health, awarded a $8.231 million Cooperative Agreement to Emory University on September 1, 2026, under the Aging Research program (CFDA 93.866) to establish the TARGET-AD Consortium, a precision medicine framework for Alzheimer's disease molecular subtyping.

The consortium integrates multi-omics data from brain and plasma samples and induced pluripotent stem cell models derived from the same individuals across multiple independent cohorts. The work aims to identify distinct molecular subtypes of Alzheimer's disease driven by unique genetic, molecular, and pathological mechanisms beyond amyloid-beta and tau pathology; uncover plasma signatures predictive of these subtypes; and prioritize subtype-specific therapeutic targets. The consortium will address gaps in prior large-scale omics studies by combining multi-tissue analyses, comprehensive multi-omics integration, and cross-cohort analysis to resolve Alzheimer's molecular heterogeneity, stratify subtypes for person-specific interventions, and provide open-access resources to accelerate therapeutic discovery.

Performance occurs in Atlanta, Georgia. The period of performance runs from September 1, 2026, through August 31, 2031.

Abstract

Overall component alzheimer's disease (ad), the leading cause of dementia in older adults, is characterized by significant biological, cellular, and pathological heterogeneity. While amyloid-beta (AΒ) plaques and TAU neurofibrillary tangles are hallmark pathologies, up to 70% of dementia cases exhibit mixed pathologies, including cerebrovascular disease, lewy bodies, and TDP-43 aggregates. Even so, these pathological markers explain only about half of the variance in cognitive decline. Genome-wide association studies (gwas) implicate pathways such as synaptic dysfunction, lipoprotein metabolism, microglial immune activation, and endothelial integrity, underscoring the need for deeper exploration of disease mechanisms. We hypothesize that distinct molecular subtypes of ad are driven by unique genetic, molecular, and pathological mechanisms, shaped by biological pathways beyond AΒ and TAU. While large-scale -omics studies have begun to subtype ad molecularly, most have been limited by single-tissue analyses, incomplete multi-omics integration, and a limited integration across multiple independent cohorts. Here we propose a highly collaborative multi-site target-ad consortium to address these gaps by integrating multi-omic data from brain and plasma samples and induced pluripotent stem cell (ipsc) models derived from the same individuals. This comprehensive approach aims to identify ad brain subtypes, uncover plasma signatures predictive of these subtypes, and prioritize subtype-specific therapeutic targets, ultimately advancing precision medicine for ad. By integrating advanced technologies and leveraging complementary multi-omic datasets from multiple independent cohorts, the target-ad consortium seeks to better resolve the molecular heterogeneity of ad, stratify subtypes for person-specific interventions, and provide open-access resources to accelerate therapeutic discovery.