Louis Elan D. author Columbia University. Center for Parkinson's Disease and Other Movement Disorders Columbia University. Epidemiology Yi Hong author Erickson-Davis Cordelia author Columbia University. Sergievsky Center Vonsattel Jean Paul author Columbia University. Pathology and Cell Biology Faust Phyllis L. author Columbia University. Pathology and Cell Biology Columbia University. Center for Parkinson's Disease and Other Movement Disorders originator text Articles 2009 manuscript version English Essential tremor (ET) is one of the most common neurological diseases. A basic understanding of its neuropathology is now emerging. Aside from Purkinje cell loss, a prominent finding is an abundance of torpedoes (rounded swellings of Purkinje cell axons). Such swellings often result from the mis-accumulation of cell constituents. Identifying the basic nature of these accumulations is an important step in understanding the underlying disease process. Torpedoes, only recently identified in ET, have not yet been characterized ultrastructurally. Light and electron microscopy were used to characterize the structural constituents of torpedoes in ET. Formalin-fixed cerebellar cortical tissue from four prospectively collected ET brains was sectioned and immunostained with a monoclonal phosphorylated neurofilament antibody (SMI-31, Covance, Emeryville, CA). Using additional sections from three ET brains, torpedoes were assessed using electron microscopy. Immunoreactivity for phosphorylated neurofilament protein revealed clear labeling of torpedoes in each case. Torpedoes were strongly immunoreactive; in many instances, two or more torpedoes were noted in close proximity to one another. On electron microscopy, torpedoes were packed with randomly arranged 10–12 nm neurofilaments. Mitochondria and smooth endoplasmic reticulum were abundant as well, particularly at the periphery of the torpedo. We demonstrated that the torpedoes in ET represent the mis-accumulation of disorganized neurofilaments and other organelles. It is not known where in the pathogenic cascade these accumulations occur (i.e., whether these accumulations are the primary event or a secondary/downstream event) and this deserves further study. Neurosciences 450 3 287 291 2009 0304-3940 http://dx.doi.org/10.1016/j.neulet.2008.11.043 http://hdl.handle.net/10022/AC:P:9906 NNC NNC 2011-03-07 15:00:38 -0500 2012-08-28 16:55:22 -0400 3029 eng