Rare diseases are difficult if not impossible to study outside of population-based registries. Particularly in the context of rare neurodegenerative diseases characterized by case heterogeneity, difficult differential diagnosis by specialists, and small numbers of patients, registries make otherwise unfeasible incidence studies cost-effective and manageable. Building up and maintaining such registries is challenging and requires strong, active, and collaborative networks. Centralization around a leading institution provides structure and consistency, but this single-site storage leads to inefficiency and bottlenecks and is prone to failures, attacks, and manipulation. Furthermore, a substantial amount of trust is required between parties sharing data in a traditional registry. Patients are increasingly reluctant to share data in light of regular news reports about healthcare data breaches. Underfunded rare disease specialized centers are also hesitant to exchange with the leading institution out of fear that the low numbers of patients may seek treatment elsewhere. A lack of electronic health records and information system interoperability in certain settings leads to information silos and only further exacerbate the other issues. Blockchain technology may provide unique, innovative solutions to many of these challenges. Specifically, through digital trust and the use of an immutable distributed ledger, automated data transaction processing, guaranteed integrity, and enhanced security, blockchain technology seems to be perfectly suitable to optimize current population-based rare neurodegenerative disease registry construction and maintenance.