Journal of the neurological sciences
-
Perry syndrome is characterized clinically by autosomal dominantly inherited, rapidly progressive parkinsonism, depression, weight loss and hypoventilation. In the seven families reported previously and the two new families presented herein (the Hawaii family and the Fukuoka-4 Japanese family), the mean disease onset age is 48 years (range: 35-61) and the mean disease duration five years (range: 2-10). Histology and immunohistochemistry show severe neuronal loss in the substantia nigra and locus coeruleus, with TDP-43-positive pathology in neurons (intranuclear and cytoplasmic inclusions, dystrophic neurites, axonal spheroids) and glial cells (glial cytoplasmic inclusions). ⋯ DCTN1 encodes p150(glued), the major subunit of the dynactin protein complex, which plays a crucial role in retrograde axonal and cytoplasmic transport of various cargoes. Evidence suggests the Perry mutations alter the binding of p150(glued) to microtubules. Further studies will examine reasons for the vulnerability of selected neuronal populations in Perry syndrome, and the link between the genetic defect and TDP-43 pathology.