Neurofilament (NF) proteins play key structural and functional roles in healthy neuronal tissues. However, in neuro-degenerative diseases aggregates of NF proteins form and this aggregation process appears to play a mechanistic role in the disease process. Because neurofilaments are obligate heteropolymers, the ability of neurofilament proteins to form filaments may depend on their domain structure. Therefore, a series of chimeric neurofilament proteins were constructed and the ability of these chimeric proteins to form filaments was tested. All were expected to form filaments with vimentin. Surprisingly, several chimeric NF constructs were unable to form filaments with vimentin. Expression of these chimeric proteins not only disassembled the existing vimentin meshwork but formed aggregates instead. The composition of these aggregates was investigated by immunofluorescence microscopy. Based on the resulting colocalization data, we conclude that these aggregates are similar to those seen in neurodegenerative diseases. Therefore, we conclude that these cell lines are a valid model system for the study of the aggregation of NF proteins and the role of these aggregates in neurodegenerative disease processes.