The presence of sodium dodecyl sulphate-stable Abeta 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, Medical Research Council Cognitive Function and Ageing Study

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211 Citations (SciVal)

Abstract

The molecular pathways leading to Alzheimer-type dementia are not well understood, but the amyloid beta-protein is believed to be centrally involved. The quantity of amyloid beta-protein containing plaques does not correlate well with clinical status, suggesting that if amyloid beta-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 beta-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 beta-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 beta-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
Original languageEnglish
Pages (from-to)1328-1341
Number of pages14
JournalBrain
Volume133
Issue number5
DOIs
Publication statusPublished - May 2010

Keywords

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Blotting, Western
  • Cerebral Cortex
  • Cohort Studies
  • Dementia
  • Drug Stability
  • Female
  • Humans
  • Immunoprecipitation
  • Male
  • Protein Multimerization
  • Sodium Dodecyl Sulfate
  • Alzheimer's disease pathology
  • biochemistry
  • cognitive impairment

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