Bridge Funding for Dominantly Inherited Alzheimer Network

Project Summary (DIAN Supplement)
This application is for bridge funding until a resubmission can be reviewed and funded maintaining
fundamental Core operations of the Dominantly Inherited Alzheimer Network (DIAN). The eight Cores of
DIAN are: Administration, Clinical, Biostatistics, Neuropathology, Biomarker, Genetics, Imaging, and
Cognition. The renewal application’s first year was budgeted for $13.1 million (total), and this supplement
application reduces the year’s funding by $4.2 million to $8.9 million (total) to maintain the essential
operations of the study which without would halt the availability of longitudinal data and resources to the
scientific community or even dissolve the entirety of the program. Bridge funding would allow for 16 sites
supported through DIAN to maintain study visits for its current active population of over 300 participants and
provide the Coordinating Center the ability to continue managing the study; support performances sites;
ensure validation and integrity to data collection, collect, manage, and handle data/tissue; and disseminate
findings and study resources to the research and medical communities. To reduce funding support, this
supplement halts all scientific project activities, limits travel costs to Coordinating Center Core members,
delays home health nurse visits for non-U.S. sites in collecting assessments and specimens, and removes in-
person family conference meeting support to the DIAN Expanded Registry (DIAN EXR). Additionally, the
ongoing DIAN-Trials Unit (DIAN-TU) Amyloid Removal Trial (ART), which has found the first clinical signs of
prevention of Alzheimer's disease in the clinic is dependent on this DIAN observational study continuing. If
gap funding is not provided, this 10 year seminal trial will be forced to stop short of demonstrating how to
prevent Alzheimer's disease.
Since its inception, the DIAN has led major scientific advances in the understanding of Alzheimer’s disease
(AD) stages, cerebrospinal fluid 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 this current funding
cycle, the DIAN updated the longitudinal progression from biochemical Aβ imbalances, through sequential
tau phosphorylations, 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).

Grant Number: 3U19AG032438-12S2
NIH Institute/Center: NIH
Principal Investigator: RANDALL BATEMAN