Familiar encephalopathy with neuroserpin inclusion bodies

We report on a new familial neurodegenerative disease with associated demen tia that has presented clinically in the fifth decade, in both genders, and in each of several generations of a large family from New York State-a pat tern of inheritance consistent with an autosomal dominant mode of transmiss ion. A key pathological finding is the presence of neuronal inclusion bodie s distributed throughout the gray matter of the cerebral cortex and in cert ain subcortical nuclei; These inclusions are distinct from any described pr eviously and henceforth are identified as Collins bodies. The Collins bodie s can be isolated by simple biochemical procedures and have a surprisingly simple composition; neuroserpin (a serine protease inhibitor) is their pred ominant component. An affinity-purified antibody against neuroserpin specif ically labels the Collins bodies, confirming their chemical composition. Th erefore, we propose a new disease entity-familial encephalopathy with neuro serpin inclusion bodies (FENIB). The conclusion that FENIB is a previously unrecognized neurodegenerative disease is supported by finding Collins bodi es in a small kindred from Oregon with familial dementia who are unrelated to the New York family. The autosomal dominant inheritance strongly suggest s that FENIB is caused by mutations in the neuroserpin gene, resulting in: intracellular accumulation of the mutant protein.