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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2011-1-4
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pubmed:abstractText |
Blood-based markers reflecting core pathological features of Alzheimer's disease (AD) in pre-symptomatic individuals are likely to accelerate the development of disease-modifying treatments. Our aim was to discover plasma proteins associated with brain amyloid-? (A?) burden in non-demented older individuals. We performed discovery-phase experiments using two dimensional gel electrophoresis (2DGE) and mass spectrometry-based proteomic analysis of plasma in combination with 11C-PiB PET imaging of the brain in samples collected 10 years prior to the PET scans. Confirmatory studies used ELISA assays in a separate set of blood samples obtained within a year of the PET scans. We observed that a panel of 18 2DGE plasma protein spots effectively discriminated between individuals with high and low brain A?. Mass spectrometry identified these proteins, many of which have established roles in A? clearance, including a strong signal from apolipoprotein-E (ApoE). In validation-phase studies, we observed a strong association between plasma ApoE concentration and A? burden in the medial temporal lobe. Targeted voxel-based analysis localized this association to the hippocampus and entorhinal cortex. APOE ?4 carriers also showed greater A? levels in several brain regions relative to ?4 non-carriers. These results suggest that both peripheral concentration of ApoE protein and APOE genotype are related to early neuropathological changes in brain regions vulnerable to AD pathology even in the non-demented elderly. Our strategy combining proteomics with in vivo brain amyloid imaging holds promise for the discovery of biologically relevant peripheral markers in those at risk for AD.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-10797593,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-10811879,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-10847596,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-11071064,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-11248079,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-11831556,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-12130773,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-12709467,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-12880848,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-14741101,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-15181253,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-15335291,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-15841309,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-15944649,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-17071923,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-17449282,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-17474819,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-17502554,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-17620873,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-17934472,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-18559859,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-18679022,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-18703614,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19025720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19064880,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19074141,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19156487,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19346482,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19398705,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19464319,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19472074,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19474427,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19640477,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19679070,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19720974,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19782124,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19840034,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19906261,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-19908146,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-20008651,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-20129318,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-20147655,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-20186853,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-20431570,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-20603455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-21228459,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-2341813,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-6474172,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-7546595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-8370587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20930274-8740983
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
1875-8908
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pubmed:author |
pubmed-author:AnYangY,
pubmed-author:CampbellJamesJ,
pubmed-author:FerrucciLuigiL,
pubmed-author:HyeAbdulA,
pubmed-author:KinseyAnnaA,
pubmed-author:LovestoneSimonS,
pubmed-author:LynhamStevenS,
pubmed-author:ResnickSusan MSM,
pubmed-author:Riddoch-ContrerasJoannaJ,
pubmed-author:SojkovaJitkaJ,
pubmed-author:ThambisettyMadhavM,
pubmed-author:TripaldiRominaR,
pubmed-author:WongDean FDF,
pubmed-author:ZhouYunY
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pubmed:issnType |
Electronic
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1099-109
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
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