Parkin-positive autosomal recessive juvenile Parkinsonism with alpha-synuclein-positive inclusions.
OBJECTIVE
To report an autopsy case of an autosomal recessive juvenile parkinsonism patient with a homozygous exon 3 deletion in the parkin gene and alpha-synuclein-positive inclusions.


METHODS
The representative areas of the brain were embedded in paraffin, stained with hematoxylin-eosin, Klüver-Barrera, and Gallyas-Braak stainings. Immunohistochemically, some of the specimens were used for immunostaining with the antibodies to alpha-synuclein, ubiquitin, and phosphorylated tau (AT8). Immunoreaction was visualized by the streptavidin-biotin-peroxidase complex method.


RESULTS
Histologically, the lesions of the brain were limited to the dopaminergic neuron system such as the substantia nigra (SN) and locus ceruleus. Melanin-containing neurons in the pars compacta of the SN were moderately to severely depleted, accompanied by gliosis. In the locus ceruleus, neurons were mildly decreased and extraneuronal melanin pigments were seen. Lewy bodies were not observed in the neuropils of the pars compacta of the SN or locus ceruleus. However, basophilic inclusion bodies were only occasionally observed in the neuropils of the pedunculopontine nucleus in the mesencephalic reticular formation. Immunohistochemistry with antibodies to alpha-synuclein and ubiquitin showed alpha-synuclein- and ubiquitin-positive inclusions in the neuropils of the pedunculopontine nucleus, which had a doughnut or round shape.


CONCLUSIONS
A variety of parkin gene abnormalities may produce pathologic differences in the degree and distribution of neuronal degeneration, including the absence or presence of Lewy bodies. A relationship between parkin-induced parkinsonism and idiopathic Parkinson disease (PD) may exist.
Sasaki
Shoichi
S
Department of Neurology, Neurologic Institute, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. ssasaki@nij.twmu.ac.jp
Shirata
Akiko
A
Yamane
Kiyomi
K
Iwata
Makoto
M
D000368:Aged; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D018740:Genetic Heterogeneity; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry*; D008543:Melanins / Q000032:analysis; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009474:Neurons / Q000737:chemistry / Q000648:ultrastructure; D010300:Parkinson Disease / Q000235:genetics; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D051843:Synucleins; D025801:Ubiquitin / Q000032:analysis; D044767:Ubiquitin-Protein Ligases / Q000032:analysis / Q000235:genetics*; D051844:alpha-Synuclein
D008543:Melanins; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D025801:Ubiquitin; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein