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The presence of sodium dodecyl sulphate-stable Aβ dimers is strongly associated with Alzheimer-type dementia

Jessica M. Mc Donald, George M. Savva, Carol Brayne, Alfred T. Welzel, Gill Forster, Ganesh M. Shankar, Dennis J. Selkoe, Paul G. Ince, Dominic M. Walsh
DOI: http://dx.doi.org/10.1093/brain/awq065 1328-1341 First published online: 19 April 2010

Summary

The molecular pathways leading to Alzheimer-type dementia are not well understood, but the amyloid β-protein is believed to be centrally involved. The quantity of amyloid β-protein containing plaques does not correlate well with clinical status, suggesting that if amyloid β-protein is pathogenic it involves soluble non-plaque material. Using 43 brains from the Newcastle cohort of the population-representative Medical Research Council Cognitive Function and Ageing Study, we examined the relationship between biochemically distinct forms of amyloid β-protein and the presence of Alzheimer-type dementia. Cortical samples were serially extracted with Tris-buffered saline, Tris-buffered saline containing 1% TX-100 and with 88% formic acid and extracts analysed for amyloid β-protein by immunoprecipitation/western blotting. The cohort was divisible into those with dementia at death with (n = 14) or without (n = 10) significant Alzheimer-type pathology, and those who were not demented (n = 19). Amyloid β-protein monomer in extracts produced using Tris-buffered saline and Tris-buffered saline containing 1% TX-100 were strongly associated with Alzheimer type dementia (P < 0.001) and sodium dodecyl sulphate-stable amyloid β-protein dimer was detected specifically and sensitively in Tris-buffered saline, Tris-buffered saline containing 1% TX-100 and formic acid extracts of Alzheimer brain. Amyloid β-protein monomer in the formic acid fraction closely correlated with diffuse and neuritic plaque burden, but was not specific for dementia. These findings support the hypothesis that soluble amyloid β-protein is a major correlate of dementia associated with Alzheimer-type pathology and is likely to be intimately involved in the pathogenesis of cognitive failure.

  • Alzheimer’s disease pathology
  • Alzheimer’s disease
  • amyloid β-protein
  • biochemistry
  • cognitive impairment
  • Abbreviations:
    Abbreviations
    amyloid β-protein
    CERAD
    Consortium to Establish a Registry for Alzheimer’s Disease
    DNAD
    dementia but no significant Alzheimer’s disease pathology
    ELISA
    enzyme-linked immunosorbent assay
    SDS
    sodium dodecyl sulphate
    TBS
    tris-buffered saline
    TBS-TX
    Tris-buffered saline containing 1% TX-100
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