Clinical and biochemical correlates of insoluble alpha-synuclein in dementia with Lewy bodies.
Alpha-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 alpha-synuclein accumulates in Parkinson's disease in a detergent insoluble form. We now examine the relationship between detergent insoluble alpha-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 alpha-synuclein enriched nearly twofold in the temporal cortex of patients with DLB compared to age-matched controls. By contrast the total amount of alpha-synuclein protein was unchanged. Surprisingly, the degree of Triton X-100 insoluble alpha-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 alpha-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.
Klucken
J
J
Department of Neurology, MassGeneral Institute for Neurodegenerative disease, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA.
Ingelsson
M
M
Shin
Y
Y
Irizarry
M C
MC
Hedley-Whyte
E T
ET
Frosch
M
M
Growdon
J
J
McLean
Pamela
P
Hyman
Bradley T
BT
D000368:Aged; D000369:Aged, 80 and over; D003902:Detergents; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000473:pathology; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D019579:Neocortex / Q000378:metabolism*; D017830:Octoxynol; D012995:Solubility; D016708:Synaptophysin / Q000378:metabolism; D013702:Temporal Lobe / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism*
D003902:Detergents; D005904:Glial Fibrillary Acidic Protein; D006360:Heat-Shock Proteins; D016708:Synaptophysin; D051844:alpha-Synuclein; D017830:Octoxynol