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 journalArticle

36 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Synucleins
Lewy Body Disease
Lewy Bodies
Octoxynol
Heat-Shock Proteins
Detergents
Parkinson Disease
Body Weights and Measures
Heat-Shock Response
Neocortex
Temporal Lobe
Dementia
Neurons

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Klucken, J., Ingelsson, M., Shin, Y., Irizarry, M. C., Hedley-Whyte, E. T., Frosch, M. P., ... Hyman, B. T. (2006). Clinical and biochemical correlates of insoluble α-synuclein in dementia with Lewy bodies. Acta Neuropathologica, 111(2), 101-108. https://doi.org/10.1007/s00401-005-0027-7

Clinical and biochemical correlates of insoluble α-synuclein in dementia with Lewy bodies. / Klucken, Jochen; Ingelsson, Martin; Shin, Youngah; Irizarry, Michael C.; Hedley-Whyte, E. T.; Frosch, Matthew P.; Growdon, John H.; McLean, Pamela J; Hyman, Bradley T.

In: Acta Neuropathologica, Vol. 111, No. 2, 02.2006, p. 101-108.

Research output: Contribution to journalArticle

Klucken, J, Ingelsson, M, Shin, Y, Irizarry, MC, Hedley-Whyte, ET, Frosch, MP, Growdon, JH, McLean, PJ & Hyman, BT 2006, 'Clinical and biochemical correlates of insoluble α-synuclein in dementia with Lewy bodies', Acta Neuropathologica, vol. 111, no. 2, pp. 101-108. https://doi.org/10.1007/s00401-005-0027-7
Klucken J, Ingelsson M, Shin Y, Irizarry MC, Hedley-Whyte ET, Frosch MP et al. Clinical and biochemical correlates of insoluble α-synuclein in dementia with Lewy bodies. Acta Neuropathologica. 2006 Feb;111(2):101-108. https://doi.org/10.1007/s00401-005-0027-7
Klucken, Jochen ; Ingelsson, Martin ; Shin, Youngah ; Irizarry, Michael C. ; Hedley-Whyte, E. T. ; Frosch, Matthew P. ; Growdon, John H. ; McLean, Pamela J ; Hyman, Bradley T. / Clinical and biochemical correlates of insoluble α-synuclein in dementia with Lewy bodies. In: Acta Neuropathologica. 2006 ; Vol. 111, No. 2. pp. 101-108.
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