title: Substantia nigra Marinesco bodies are associated with decreased striatal expression of dopaminergic markers.
abstract: Marinesco bodies are nuclear inclusions found in pigmented neurons of the substantia nigra and locus ceruleus of humans and monkeys. It has long been known that the frequency of these inclusions increases with advancing age, but no pathologic associations have ever been established. We quantified Marinesco body frequency in human autopsy subjects, classified as young normal controls, elderly controls, dementia with Lewy bodies (DLB), Alzheimer disease (AD), and Parkinson disease (PD). Elderly controls, AD cases, and DLB cases had significantly increased Marinesco body frequencies relative to young controls and DLB cases had significantly increased frequencies relative to elderly controls, while PD cases did not differ from young controls; cases with AD did not differ from elderly controls. Lewy body-containing neurons had significantly higher Marinesco body frequencies than non-Lewy body-containing neurons. Marinesco body frequency in elderly control cases correlated significantly, in inverse fashion, with striatal concentrations of the dopaminergic neuron markers dopamine transporter and tyrosine hydroxylase. These statistical associations suggest that Marinesco bodies constitute or mark a pathologic process that may be related to, or contribute to, age-related motor dysfunction and/or Lewy body disorders. Further studies are needed to ascertain the molecular basis of Marinesco body formation; preliminary studies indicate that proteasome dysfunction can lead to similar abnormalities in cultured cells.
authors.affiliation: Sun Health Research Institute, Sun City, Arizona 85372, USA. thomas.beach@sunhealth.org
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Walker
authors.forename: Lucia I
authors.initials: LI
authors.lastname: Sue
authors.forename: Amanda
authors.initials: A
authors.lastname: Newell
authors.forename: Charles C
authors.initials: CC
authors.lastname: Adler
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Joyce
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D015151:Immunoblotting; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D016716:PC12 Cells; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D051381:Rats; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine