Clinical and biochemical correlates of insoluble α-synuclein in dementia with Lewy bodies

Jochen Klucken, Martin Ingelsson, Youngah Shin, Michael C. Irizarry, E. T. Hedley-Whyte, Matthew P. Frosch, John H. Growdon, Pamela J. McLean, Bradley T. Hyman

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

α-Synuclein is a major constituent of Lewy bodies, the fibrillar aggregates that form within neurons in Parkinson's disease and dementia with Lewy bodies (DLB). Recent biochemical data show that α-synuclein accumulates in Parkinson's disease in a detergent insoluble form. We now examine the relationship between detergent insoluble α-synuclein and the presence of Lewy bodies, clinical measures of dementia and biochemical parameters in a series of individuals with DLB. We found that Triton X-100 insoluble α-synuclein enriched nearly twofold in the temporal cortex of patients with DLB compared to age-matched controls. By contrast the total amount of α-synuclein protein was unchanged. Surprisingly, the degree of Triton X-100 insoluble α-synuclein did not correlate with either the duration of illness or the number of Lewy bodies counted using stereological methods from an adjacent block of tissue. However, the Triton X-100 soluble fraction of α-synuclein did correlate strongly with the expression of several heat shock proteins (HSPs) in DLB but not control cases, suggesting a coordinated HSP response in DLB neocortex.

Original languageEnglish (US)
Pages (from-to)101-108
Number of pages8
JournalActa neuropathologica
Volume111
Issue number2
DOIs
StatePublished - Feb 2006

Keywords

  • Heat shock proteins
  • Lewy body dementia
  • α-Synuclein

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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