APOLIPOPROTEIN-E AND APOLIPOPROTEIN-E MESSENGER-RNA IN MUSCLE OF INCLUSION-BODY MYOSITIS AND MYOPATHIES

Sporadic inclusion body myositis and the hereditary inclusion body myo pathies are severe, progressive muscle diseases, characterized patholo gically by vacuolated muscle fibers containing paired helical filament s. We immunostained muscle biopsy specimens from sporadic inclusion bo dy myositis, hereditary inclusion body myopathy disease control, and n ormal patients with several antibodies against apolipoprotein E (ApoE) . Approximately 80 to 90% of the vacuolated muscle fibers of sporadic inclusion body myositis contained well-defined, strongly immunoreactiv e ApoE inclusions. In hereditary inclusion body myopathy only rare vac uolated fibers had immunoreactive inclusions, whereas most had diffuse cytoplasmic ApoE immunoreactivity. Ultrastructurally, ApoE immunoreac tivity in sporadic myositis was localized mainly to the paired helical filaments. By contrast, in the hereditary form, ApoE immunoreactivity occurred on material in close proximity to the paired helical filamen ts, but never was on the paired helical filaments. In both muscle dise ases, ApoE was also on the 6- to 10-Mm filaments and amorphous materia l. In the sporadic form, ApoE-immunoreactive deposits colocalized with Congo red-positive deposits; however, in muscle fibers from patients with hereditary disease there was no congophilia. ApoE messenger RNA w as not detectable in muscle fibers from patients with hereditary or sp oradic disease but was expressed abundantly in muscle macrophages. In all control and inclusion body myositis or myopathy biopsy specimens, ApoE immunoreactivity was strong at the postsynaptic domain of neuromu scular junctions; nonjunctional regions of normal fibers were negative for ApoE. ApoE immunoreactivity occurred diffusely in regenerating mu scle fibers, a subset of which had detectable ApoE messenger RNA.