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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 5
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pubmed:dateCreated |
2010-4-26
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pubmed:abstractText |
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 < 0.001) and sodium dodecyl sulphate-stable amyloid beta-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 beta-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 beta-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.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20403962-10393832,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20403962-10415140,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20403962-10487842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20403962-10589538,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20403962-10978169,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20403962-12130773,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20403962-1311804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20403962-15984012,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20403962-17286590,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20403962-9916941
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1460-2156
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
133
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1328-41
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pubmed:dateRevised |
2011-7-28
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pubmed:meshHeading |
pubmed-meshheading:20403962-Aged,
pubmed-meshheading:20403962-Aged, 80 and over,
pubmed-meshheading:20403962-Alzheimer Disease,
pubmed-meshheading:20403962-Amyloid beta-Peptides,
pubmed-meshheading:20403962-Blotting, Western,
pubmed-meshheading:20403962-Cerebral Cortex,
pubmed-meshheading:20403962-Cohort Studies,
pubmed-meshheading:20403962-Dementia,
pubmed-meshheading:20403962-Drug Stability,
pubmed-meshheading:20403962-Female,
pubmed-meshheading:20403962-Humans,
pubmed-meshheading:20403962-Immunoprecipitation,
pubmed-meshheading:20403962-Male,
pubmed-meshheading:20403962-Protein Multimerization,
pubmed-meshheading:20403962-Sodium Dodecyl Sulfate
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pubmed:year |
2010
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pubmed:articleTitle |
The presence of sodium dodecyl sulphate-stable Abeta dimers is strongly associated with Alzheimer-type dementia.
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pubmed:affiliation |
Laboratory for Neurodegenerative Research, School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin 4, Republic of Ireland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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