title: Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques.
abstract: In neurodegenerative disorders, such as Parkinson's disease (PD), alpha-synuclein (α-syn) accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB). This α-syn-related pathology is termed synucleinopathy. It remains unclear how α-syn accumulation expands during the progress of synucleinopathy in the human brain. In our study, we investigated the patterns of distribution and propagation of forebrain neurons expressing α-syn in aged macaques. It was found that the occurrence of α-syn-positive neurons proceeded topologically based on the midbrain dopamine pathways arising from the substantia nigra and the ventral tegmental area where they were primarily observed. In the nigrostriatal or mesolimbic dopamine pathway, the age-dependent increase in α-syn-positive neurons was evident in the striatum or the nucleus accumbens, respectively. Concerning the nigrostriatal pathway, a mediolateral or rostrocaudal gradient was seen in the substantia nigra or the striatum, respectively, and a compensatory increase in dopamine transporter occurred in the striatum regardless of the decreased dopamine level. In the mesocortical dopamine pathway, α-syn-positive neurons appeared in the prefrontal and then motor areas of the frontal lobe. Given that neither LB formation nor clinical phenotype manifestation was detected in any of the monkeys examined in the present study, aged macaques may be useful as a potential presymptomatic model for PD and LB-related neuropsychiatric disorders.
authors.affiliation: Systems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, Aichi, Japan.|Department of Neurology and Stroke Medicine, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Katsuo
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Systems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, Aichi, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Inoue
authors.affiliation: Department of Neurology and Stroke Medicine, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.|Department of Neurology and Stroke Center, University Hospital Mizonokuchi, School of Medicine, Teikyo University, Kawasaki, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kuroiwa
authors.affiliation: Department of Neurology and Stroke Medicine, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.affiliation: Systems Neuroscience Section, Primate Research Institute, Kyoto University, Inuyama, Aichi, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takada
mesh_terms: D000367:Age Factors; D000818:Animals; D002452:Cell Count; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D008251:Macaca; D008297:Male; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D016548:Prosencephalon / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D013378:Substantia Nigra / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine