PROJECT SUMMARY/ABSTRACT Down syndrome (DS) is caused by the inheritance of three rather than the expected two copies of chromosome 21, or trisomy 21. DS is characterized by specific structural abnormalities in the brain, by a range of cognitive deficits and intellectual disability, and by a significantly high risk of developing Alzheimer disease by middle age. The rapid pace of progress in DS research that has taken place in the last decade highlights the critical need for effective communication between scientists, clinicians, families and self-advocates to take basic research discoveries from the laboratory to clinical trials that benefit people with DS. Advances in DS research are not only driven by senior scientists but are dependent up on the nurturing of our next generation of junior scientists. Thus, this application requests funding to cover travel expenses of American-based junior investigators, postdoctoral fellows and graduate students to attend the Fourth International conference of the Trisomy 21 Research Society (T21RS). Attendees at this meeting will include established DS and non-DS investigators whose research directly or indirectly informs critical aspects of DS cognition, neuropathology, translational opportunities and clinical trials. The meeting will take place in Long Beach, California from June 8 to June 12, 2022. Based on our previous successes, we anticipate that this conference will lead to fruitful discussions and novel collaborations that are essential to define the future of DS research. The theme of our meeting will be Imagine, Discover, Inspire.