Quantitative proteomics identifies surfactant-resistant α-synuclein in cerebral cortex of Parkinsonism-dementia complex of Guam but not Alzheimer's disease or progressive supranuclear palsy

Wan Yang, Randall (Randy) Woltjer, Izabela Sokal, Catherine Pan, Yan Wang, Mary Brodey, Elaine R. Peskind, James B. Leverenz, Jing Zhang, Daniel P. Perl, Douglas R. Galasko, Thomas J. Montine

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Parkinsonism-dementia complex (PDC) remains a significant health burden to the Chamorro population. We tested the hypothesis that quantitative proteomics might provide fresh insight into this enigmatic illness by analyzing proteins resistant to surfactant extraction from patients with Alzheimer's disease (AD) or PDC and then-matched controls using isobaric tags for relative and absolute quantification. In addition to the expected increase in abnormal frontal cortical Aβ peptides, tau, ubiquitin, and apolipoprotein E in AD, and tau in PDC, we identified α-synuclein (SNCA) as a major abnormal protein in PDC but not AD. We confirmed our isobaric tags for relative and absolute quantification findings by enzyme-linked immunosorbent assay in frontal and temporal cortices. We extended our assays to include a limited number of cases of progressive supranuclear palsy (PSP) and dementia with Lewy bodies; we observed increased abnormal tau but not SNCA in PSP, and abnormal SNCA in dementia with Lewy bodies that was quantitatively similar to PDC. Finally, soluble Aβ oligomers were selectively increased in AD but not PDC or PSP. These results show that frontal and temporal cortex in PDC is distinguished from AD and PSP by its accumulation of abnormal SNCA and suggest that PDC be considered a synucleinopathy as well as a tauopathy.

Original languageEnglish (US)
Pages (from-to)993-1002
Number of pages10
JournalAmerican Journal of Pathology
Volume171
Issue number3
DOIs
StatePublished - Sep 2007
Externally publishedYes

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Synucleins
Guam
Progressive Supranuclear Palsy
Parkinsonian Disorders
Surface-Active Agents
Cerebral Cortex
Proteomics
Dementia
Alzheimer Disease
Lewy Body Disease
Frontal Lobe
Temporal Lobe
Tauopathies
Apolipoproteins E
Ubiquitin
Proteins
Enzyme-Linked Immunosorbent Assay
Peptides

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Quantitative proteomics identifies surfactant-resistant α-synuclein in cerebral cortex of Parkinsonism-dementia complex of Guam but not Alzheimer's disease or progressive supranuclear palsy. / Yang, Wan; Woltjer, Randall (Randy); Sokal, Izabela; Pan, Catherine; Wang, Yan; Brodey, Mary; Peskind, Elaine R.; Leverenz, James B.; Zhang, Jing; Perl, Daniel P.; Galasko, Douglas R.; Montine, Thomas J.

In: American Journal of Pathology, Vol. 171, No. 3, 09.2007, p. 993-1002.

Research output: Contribution to journalArticle

Yang, Wan ; Woltjer, Randall (Randy) ; Sokal, Izabela ; Pan, Catherine ; Wang, Yan ; Brodey, Mary ; Peskind, Elaine R. ; Leverenz, James B. ; Zhang, Jing ; Perl, Daniel P. ; Galasko, Douglas R. ; Montine, Thomas J. / Quantitative proteomics identifies surfactant-resistant α-synuclein in cerebral cortex of Parkinsonism-dementia complex of Guam but not Alzheimer's disease or progressive supranuclear palsy. In: American Journal of Pathology. 2007 ; Vol. 171, No. 3. pp. 993-1002.
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