This NOFO would support investigations with a minimum of two relevant co-pathologies (e.g., tau, alpha-synuclein, TDP-43, TMEM106B, vascular), with optional risk factors and co-morbidities, to identify cellular and molecular mechanisms of how/why multi-proteinopathy interactions drive worsening neurodegenerative
processes and phenotypic outcomes.
Studies should examine co-pathology cellular and molecular interactions across brain regions and time in proximate cell population, across various intracellular dynamics and localization, and upstream and downstream from aggregated protein states to determine what events lead to worse phenotypic outcomes.