The Alzheimer's Disease Related Dementias (ADRD) Summits (convened by the NINDS in 2013, 2016, and 2019) recommend the collection of source cells and induced pluripotent stem cell (iPSC) lines from patients with ADRDs (Frontotemporal Dementia (FTD), Lewy Body Dementia (LBD), Vascular contributions to Cognitive Impairment and Dementia (VCID), and Multiple Etiology Dementias). Along with linked de-identified clinical data, these resources are to be shared broadly with the scientific research community by both NIH funded researchers, by the ADRD research community at large, and through the NINDS Human Cell and Data Repository (NHCDR) - an NINDS funded repository that serves as a resource to both academic and industry investigators to advance basic and translational research in neurological disorders.

The purpose of this Notice of Special Interest (NOSI) is to encourage submission of applications for administrative supplements to provide deep quality control and molecular phenotyping of ADRD iPSC lines to enable the study of how genetic variants influence on convergent ADRD disease pathways. The funds from these Administrative Supplements are intended to support research activities on existing ADRD iPSCs (including isogenic control and edited lines) and their source cell lines including: (1) Whole Genome Sequencing (WGS), (2) RNA-Sequencing (RNA-seq) and (3) DNA methylation profiling. WGS will be used to identify the fraction of variability derived from the genetic background of the iPSC lines. Transcriptomic and methylation profiling will provide additional insight into drivers of iPSC variability such as epigenetic state and determine whether somatic mutations occurring during reprogramming have functional consequences in gene expression patterns. The generation of systematically derived ADRD iPSC resources associated with well-characterized and standardized genomic, transcriptomic and epigenomic profiling will aid in validating the quality and integrity of the cell lines as well provide a vital resource in interrogating the genetic contribution to underlying ADRD disease mechanisms.

Only supplement applications to parent awards that have an NS designation for NIH institute and are active (i.e., not in a no-cost or funded extension) are eligible for support under this NOSI.

Application Due Date(s) – May 5, 2021

NOT-NS-21-041