The Center for Neurodegenerative Disease Research (CNDR), a research consortium at the University of Pennsylvania investigating the causes and mechanisms of neurodegenerative diseases, has archived its 2000th case in its brain bank. The CNDR was founded by Virginia M.-Y. Lee, PhD, MBA, and John Q. Trojanowski, MD, PhD, who founded and co-directed the CNDR until 2002. The first case in the CNDR archive was banked by Dr. Trojanowski in 1985. The brain bank was maintained over the years with the help of countless people, including Terry Schuck, John Robinson, Kevin Davies, Joe Dirienzi, Igor Tsimberg, Mark Forman and many others who have helped administer, harvest, cut, store, section, stain and diagnose each case. The brain bank has grown, not only in size but in complexity, as each case is now associated with deep clinical, genetic, biomarker, and neuroimaging data. The brain bank is widely regarded as a premier collection and has supported historic discoveries, including the demonstration that tau is the major constituent of neurofibrillary tangles, that Lewy bodies are comprised of alpha-synuclein, and that inclusions in FTLD and ALS are made of TDP-43 protein. Coupled with the biochemical fractionation protocols developed by Dr. Virginia Lee, these brain tissues have been instrumental in supporting the hypothesis that neurodegenerative disease proteinopathy transmits through the brain connectome. For decades, the CNDR brain bank has supported research within Penn, across the nation, and internationally.