Lack of evidence for Nocardia asteroides in brain specimens from Lewy body-containing disorders.

Previous studies have suggested that Nocardia asteroides may play a role in the pathogenesis of Parkinson's disease (PD), including the production of Lewy bodies, the inclusion bodies present in this disorder. This study explored the possible connection between Nocardia and two Lewy body-containing disorders, PD and dementia with Lewy bodies (DLB). Substantia nigra specimens from individuals with PD, DLB, other neurodegenerative disorders, and normal subjects were evaluated for nocardial infection by in situ hybridization, PCR, and Gram staining. Brain specimens from a cynomolgus monkey experimentally infected with N. asteroides for 48 h served as the controls for in situ hybridization and Gram staining, and a nocardial pellet was the PCR control. The organism was detected by in situ hybridization and Gram stain in the experimentally infected monkey brain, and by PCR from the nocardial pellet. However, in situ hybridization reactivity was detected in only three of the 125 human brain specimens (2.4%; one case each of PD, DLB, and Alzheimer's disease), and none of the specimens was positive for Nocardia by PCR or Gram staining. These findings do not support an association of Nocardia with Lewy body-containing disorders.

In situ hybridization for detection of nocardial 16S rRNA: reactivity within intracellular inclusions in experimentally infected cynomolgus monkeys--and in Lewy body-containing human brain specimens.

Our previous studies found that experimental infection of BALB/c mice with the Gram-positive bacterium Nocardia asteroides induced a parkinsonian-type syndrome with levodopa-responsive movement abnormalities, loss of nigrostriatal dopaminergic neurons, depletion of striatal dopamine, and intraneuronal inclusions in the substantia nigra (SN) with an appearance similar to Lewy bodies. In the present study, an in situ hybridization technique was developed to detect nocardial 16S ribosomal RNA (rRNA), using a Nocardia-specific probe (B77). Cerebral cortical specimens from cynomolgus monkeys were examined for the presence of nocardial RNA 48 h, 3.5 months, and 1 year after experimental infection with N. asteroides. Hybridization reactions were detected within Nocardia-like structures 48 h after infection and within intracellular inclusion bodies (immunoreactive for alpha-synuclein and ubiquitin) in one of two 3.5-month-infected monkeys. The in situ hybridization procedure was then applied in a blinded fashion to 24 human SN specimens with Lewy bodies and 11 human SN specimens without Lewy bodies (including five normal controls). Hybridization reactions were detected in nine Lewy body-containing specimens and none of the others. Reactivity was limited to inclusions with the appearance of Lewy bodies, with the exception of one specimen in which intracellular reactivity was also observed in Nocardia-like structures. These results suggest a possible association between Nocardia and neurodegenerative disorders in which Lewy bodies are present.