Dominantly inherited alzheimer network - overall/overview summary since its initial funding in 2008, the dominantly inherited alzheimer network (dian) has led major scientific advances in the…

The National Institute on Aging awarded a $9.563 million Cooperative Agreement to The Washington University on September 1, 2026, under the Aging Research program (CFDA 93.866) to support the Dominantly Inherited Alzheimer Network (DIAN).

DIAN will conduct longitudinal biomarker research and clinical studies focused on autosomal dominant Alzheimer's disease (ADAD). The network will validate the amyloid-tau-neurodegeneration (ATN) framework using plasma biomarkers across genetically and environmentally diverse populations; expand recruitment to double the active cohort and increase longitudinal sampling to identify genetic and exposome modifiers of disease onset and decline; and discover and validate therapeutic targets beyond amyloid and tau. DIAN will expand recruitment across Central and South America to include participants with lower socioeconomic status and education, incorporate rural and urban cohorts, implement home-based assessments and blood collection, and integrate a scientific project for novel target discovery.

The period of performance runs from September 1, 2026, through August 31, 2031. Work is performed in University City, Missouri. The Aging Research program supports biomedical, social, and behavioral research directed toward understanding the aging process and diseases affecting older populations, with emphasis on preventing and treating Alzheimer's disease and related dementias.

Dominantly inherited alzheimer network - overall/overview summary since its initial funding in 2008, the dominantly inherited alzheimer network (dian) has led major scientific advances in the understanding of alzheimer's disease (ad) stages, CSF and plasma biomarkers, mechanistic links to therapeutic targets, and enabled ground-breaking prevention and interventional trials. Dian has helped define the sequence, timing, and magnitude of longitudinal ad biomarker changes decades before symptoms begin. This work directly led to the development and implementation of primary and secondary prevention trials for autosomal dominant ad (adad) and the validation of the amyloid-TAU- neurodegeneration (ATN) criteria. In its prior funding cycle, the dian OBS updated the longitudinal progression from biochemical AΒ imbalances, through sequential TAU phosphorylation, to the emergence of TAU pathology with symptom onset. This TAU staging signature of ad can now be tracked with specific biomarkers and was confirmed in "sporadic" late onset ad (load). In this application, we build on these advances to address NIH milestones to further understand major contributors to disease progression, resilience and heterogeneity and target validation for future therapeutics. Major goals of dian include: 1) validate the ATN framework using plasma biomarkers in genetically and environmentally diverse populations, 2) double the active cohort and increase longitudinal sampling to identify genetic and exposome modifiers of onset and decline, and 3) discover and validate targets beyond amyloid and TAU to inform therapeutic development. We will accomplish these goals through many innovative initiatives: expanding recruitment across central and south america, including participants with lower socioeconomic status and education, incorporating rural and urban cohorts, implementing home- based assessments and blood collection, and integrating a scientific project aimed at novel target discovery. We will accelerate these groundbreaking discoveries within dian OBS and the broader scientific community through an enhanced data resource and sharing plan leveraging the resources of the alzheimer's disease data initiative (addi) and global neurodegenerative proteomic collaboration (gnpc). We will examine the hypothesis that adad progresses through distinct clinical, imaging, and biomarker- defined stages, including blood-based biomarkers, and that transitions between these stages reflect shifts in molecular pathways. We further posit that integrating molecular-to-brain measures from asymptomatic adad will reveal and validate diagnostic and therapeutic targets applicable to load, and that studying heterogeneity across families and mutation types will uncover mechanisms of risk and resilience. To test this, we will (1) use blood-based biomarkers to validate ATN framework progression established in CSF, and (2) identify and validate novel therapeutic targets.