biostudies-literaturePetrlova JNIA NIH HHSU.S. National Institutes of HealthNIGMS NIH HHS402-16https://www.ebi.ac.uk/biostudies/studies/S-EPMC3016465biostudies-literatureUnknown79(2)The molecular pathogenesis of disorders arising from protein misfolding and aggregation is difficult to elucidate, involving a complex ensemble of intermediates, whose toxicity depends upon their state of progression along distinct processing pathways. To address the complex misfolding and aggregation that initiates the toxic cascade resulting in Alzheimer's disease (AD), we have developed a 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid spin-labeled amyloid-β (Aβ) peptide to observe its isoform-dependent interaction with the apoE protein. Although most individuals carry the E3 isoform of apoE, ∼15% of humans carry the E4 isoform, which is recognized as the most significant genetic determinant for Alzheimer's. ApoE is consistently associated with the amyloid plaque marker fProteinsA differential association of Apolipoprotein E isoforms with the amyloid-β oligomer in solution.PMC3016465R01 AG029246-04R01 AG029246-03AG031362R01 GM080542R01 AG029246-05AG010129R01 AG029246-02R01 AG029246-01A1R01 AG029246Hong HSHarishchandra GBricarello DALorigan GAPetrlova JVoss JCJin LWfalseA differential association of Apolipoprotein E isoforms with the amyloid-β oligomer in solution.The molecular pathogenesis of disorders arising from protein misfolding and aggregation is difficult to elucidate, involving a complex ensemble of intermediates, whose toxicity depends upon their state of progression along distinct processing pathways. To address the complex misfolding and aggregation that initiates the toxic cascade resulting in Alzheimer's disease (AD), we have developed a 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid spin-labeled amyloid-β (Aβ) peptide to observe its isoform-dependent interaction with the apoE protein. Although most individuals carry the E3 isoform of apoE, ∼15% of humans carry the E4 isoform, which is recognized as the most significant genetic determinant for Alzheimer's. ApoE is consistently associated with the amyloid plaque marker f2011-01-01T00:00:00Z2011 Feb2025-04-04T19:18:36.356Z2019-03-27T00:37:52ZS-EPMC30164652106987010.1002/prot.22891