Abnormal accumulation of proteins in filamentous cytoplasmic inclusions is a hallmark of several neurodegenerative disorders, including Alzheimer disease (AD) and Pick disease (PD). Musashi-1 (Msi-1), an RNA-binding protein associated with neural progenitor cells, has been shown by others to increase the accumulation of tau isoforms in intracellular inclusions in frontotemporal dementia and parkinsonism linked to chromosome 17. We investigated the expression of Msi-1 in the hippocampus of AD, PD, and aged normal control subjects using immunohistochemistry. Comparison of immediately adjacent serial sections stained using the modified Bielschowsky method and immunostained for Msi-1 showed that Msi-1 was present in 83 +/- 6% of neurofibrillary tangle bearing neurons in AD and 94 +/- 14% of Pick bodies in PD specimens. Aged control hippocampus demonstrated virtually no Msi-1 immunostaining. The presence of Msi-1 in a significant percentage of neurons containing cytoplasmic inclusions in 2 different neurodegenerative diseases suggests that it may play a role in the pathogenesis of these lesions.