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Interaction between α-synuclein and tau in Parkinson's disease comment on Wills et al.: elevated tauopathy and α-synuclein pathology in postmortem Parkinson's disease brains with and without dementia. Exp Neurol 2010; 225: 210-218.
Exp Neurol. 2011 Jan; 227(1):13-8.EN

Abstract

Recent neurochemical studies in postmortem brains of patients with Parkinson's disease (PD), PD with dementia (PDD) and age-matched controls revealed significant decrease of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in striatum, confirming previous studies indicating substantial loss of dopaminergic neurons and terminals. Insoluble α-synuclein (αSyn) was significantly increased in both striata and inferior frontal gyrus (IFG), more severe in PDD, probably related to Lewy body (LB) burden discussed as one cause of dementia in PD. Parkin levels frequently related to recessive and young-onset PD were unchanged, suggesting no link to sporadic PD. Novel and most interesting data showed elevated tauopathy in striata of both PD and PDD, associated with increased levels of phosphorylated GSK-3β and reduced 20S proteasomal subunits but - despite increased cortical αSyn - unchanged pTau in IFG, related to increased pGSK-3β and decreased 19S proteasome subunits. These data, recently confirmed in PDGF-αSyn transgenic mice (Haggerty et al., submitted) suggest tauopathy in PD and PDD restricted to the dopaminergic nigrostriatal system and in various animal models of PD show topographic differences from a global tauopathy in Alzheimer's disease (AD) (and other tauopathies). Although some of these data are at variance to current neuropathologic findings in PD and PDD, they confirm frequently discussed correlations/overlaps between AD and PD/PDD and synergistic effects of αSyn, pTau, β-amyloid, and other pathologic proteins, suggesting a dualism or triad of neurodegeneration, the basic molecular pathogenesis remains to be elucidated.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Jellinger KA
Institute of Clinical Neurobiology, A 1070, Vienna, Austria. kurt.jellinger@univie.ac.at

MeSH

BrainDementiaHumansIntermediate Filament ProteinsParkinson DiseasePostmortem Changestau Proteins

Pub Type(s)

Comment
Journal Article

Language

eng

PubMed ID

20965169

Citation

Jellinger, Kurt A.. "Interaction Between Α-synuclein and Tau in Parkinson's Disease Comment On Wills Et Al.: Elevated Tauopathy and Α-synuclein Pathology in Postmortem Parkinson's Disease Brains With and Without Dementia. Exp Neurol 2010; 225: 210-218." Experimental Neurology, vol. 227, no. 1, 2011, pp. 13-8.
Jellinger KA. Interaction between α-synuclein and tau in Parkinson's disease comment on Wills et al.: elevated tauopathy and α-synuclein pathology in postmortem Parkinson's disease brains with and without dementia. Exp Neurol 2010; 225: 210-218. Exp Neurol. 2011;227(1):13-8.
Jellinger, K. A. (2011). Interaction between α-synuclein and tau in Parkinson's disease comment on Wills et al.: elevated tauopathy and α-synuclein pathology in postmortem Parkinson's disease brains with and without dementia. Exp Neurol 2010; 225: 210-218. Experimental Neurology, 227(1), 13-8. https://doi.org/10.1016/j.expneurol.2010.10.006
Jellinger KA. Interaction Between Α-synuclein and Tau in Parkinson's Disease Comment On Wills Et Al.: Elevated Tauopathy and Α-synuclein Pathology in Postmortem Parkinson's Disease Brains With and Without Dementia. Exp Neurol 2010; 225: 210-218. Exp Neurol. 2011;227(1):13-8. PubMed PMID: 20965169.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interaction between α-synuclein and tau in Parkinson's disease comment on Wills et al.: elevated tauopathy and α-synuclein pathology in postmortem Parkinson's disease brains with and without dementia. Exp Neurol 2010; 225: 210-218. A1 - Jellinger,Kurt A, Y1 - 2010/10/20/ PY - 2010/09/23/received PY - 2010/10/12/accepted PY - 2010/10/23/entrez PY - 2010/10/23/pubmed PY - 2011/2/5/medline SP - 13 EP - 8 JF - Experimental neurology JO - Exp Neurol VL - 227 IS - 1 N2 - Recent neurochemical studies in postmortem brains of patients with Parkinson's disease (PD), PD with dementia (PDD) and age-matched controls revealed significant decrease of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in striatum, confirming previous studies indicating substantial loss of dopaminergic neurons and terminals. Insoluble α-synuclein (αSyn) was significantly increased in both striata and inferior frontal gyrus (IFG), more severe in PDD, probably related to Lewy body (LB) burden discussed as one cause of dementia in PD. Parkin levels frequently related to recessive and young-onset PD were unchanged, suggesting no link to sporadic PD. Novel and most interesting data showed elevated tauopathy in striata of both PD and PDD, associated with increased levels of phosphorylated GSK-3β and reduced 20S proteasomal subunits but - despite increased cortical αSyn - unchanged pTau in IFG, related to increased pGSK-3β and decreased 19S proteasome subunits. These data, recently confirmed in PDGF-αSyn transgenic mice (Haggerty et al., submitted) suggest tauopathy in PD and PDD restricted to the dopaminergic nigrostriatal system and in various animal models of PD show topographic differences from a global tauopathy in Alzheimer's disease (AD) (and other tauopathies). Although some of these data are at variance to current neuropathologic findings in PD and PDD, they confirm frequently discussed correlations/overlaps between AD and PD/PDD and synergistic effects of αSyn, pTau, β-amyloid, and other pathologic proteins, suggesting a dualism or triad of neurodegeneration, the basic molecular pathogenesis remains to be elucidated. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/20965169/Interaction_between_α_synuclein_and_tau_in_Parkinson's_disease_comment_on_Wills_et_al_:_elevated_tauopathy_and_α_synuclein_pathology_in_postmortem_Parkinson's_disease_brains_with_and_without_dementia__Exp_Neurol_2010 DB - PRIME DP - Unbound Medicine ER -