Self-Propagative Replication of Aβ Oligomers Suggests Potential Transmissibility in Alzheimer Disease
Identifieur interne : 001090 ( Pmc/Curation ); précédent : 001089; suivant : 001091Self-Propagative Replication of Aβ Oligomers Suggests Potential Transmissibility in Alzheimer Disease
Auteurs : Amit Kumar [États-Unis] ; Kayla M. Pate [États-Unis] ; Melissa A. Moss [États-Unis] ; Dexter N. Dean [États-Unis] ; Vijayaraghavan Rangachari [États-Unis]Source :
- PLoS ONE [ 1932-6203 ] ; 2014.
Abstract
The aggregation of amyloid-β (Aβ) peptide and its deposition in parts of the brain form the central processes in the etiology of Alzheimer disease (AD). The low-molecular weight oligomers of Aβ aggregates (2 to 30 mers) are known to be the primary neurotoxic agents whose mechanisms of cellular toxicity and synaptic dysfunction have received substantial attention in the recent years. However, how these toxic agents proliferate and induce widespread amyloid deposition throughout the brain, and what mechanism is involved in the amplification and propagation of toxic oligomer species, are far from clear. Emerging evidence based on transgenic mice models indicates a transmissible nature of Aβ aggregates and implicates a prion-like mechanism of oligomer propagation, which manifests as the dissemination and proliferation of Aβ toxicity. Despite accumulating evidence in support of a transmissible nature of Aβ aggregates, a clear, molecular-level understanding of this intriguing mechanism is lacking. Recently, we reported the characterization of unique replicating oligomers of Aβ42 (12–24 mers)
Url:
DOI: 10.1371/journal.pone.0111492
PubMed: 25365422
PubMed Central: 4218758
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<front><div type="abstract" xml:lang="en"><p>The aggregation of amyloid-β (Aβ) peptide and its deposition in parts of the brain form the central processes in the etiology of Alzheimer disease (AD). The low-molecular weight oligomers of Aβ aggregates (2 to 30 mers) are known to be the primary neurotoxic agents whose mechanisms of cellular toxicity and synaptic dysfunction have received substantial attention in the recent years. However, how these toxic agents proliferate and induce widespread amyloid deposition throughout the brain, and what mechanism is involved in the amplification and propagation of toxic oligomer species, are far from clear. Emerging evidence based on transgenic mice models indicates a transmissible nature of Aβ aggregates and implicates a prion-like mechanism of oligomer propagation, which manifests as the dissemination and proliferation of Aβ toxicity. Despite accumulating evidence in support of a transmissible nature of Aβ aggregates, a clear, molecular-level understanding of this intriguing mechanism is lacking. Recently, we reported the characterization of unique replicating oligomers of Aβ42 (12–24 mers) <italic>in</italic>
<italic>vitro</italic>
called <underline>L</underline>
arge <underline>F</underline>
atty <underline>A</underline>
cid-derived <underline>O</underline>
ligomers (LFAOs) (Kumar et al., 2012, <italic>J. Biol. Chem</italic>
). In the current report, we establish that LFAOs possess physiological activity by activating NF-κB in human neuroblastoma cells, and determine the experimental parameters that control the efficiency of LFAO replication by self-propagation. These findings constitute the first detailed report on monomer – oligomer lateral propagation reactions that may constitute potential mechanism governing transmissibility among Aβ oligomers. These data support the previous reports on transmissible mechanisms observed in transgenic animal models.</p>
</div>
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<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Walsh, Dm" uniqKey="Walsh D">DM Walsh</name>
</author>
<author><name sortKey="Tseng, Bp" uniqKey="Tseng B">BP Tseng</name>
</author>
<author><name sortKey="Rydel, Re" uniqKey="Rydel R">RE Rydel</name>
</author>
<author><name sortKey="Podlisny, Mb" uniqKey="Podlisny M">MB Podlisny</name>
</author>
<author><name sortKey="Selkoe, Dj" uniqKey="Selkoe D">DJ Selkoe</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Klein, Wl" uniqKey="Klein W">WL Klein</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Walsh, Dm" uniqKey="Walsh D">DM Walsh</name>
</author>
<author><name sortKey="Klyubin, I" uniqKey="Klyubin I">I Klyubin</name>
</author>
<author><name sortKey="Fadeeva, Jv" uniqKey="Fadeeva J">JV Fadeeva</name>
</author>
<author><name sortKey="Cullen, Wk" uniqKey="Cullen W">WK Cullen</name>
</author>
<author><name sortKey="Anwyl, R" uniqKey="Anwyl R">R Anwyl</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lacor, Pn" uniqKey="Lacor P">PN Lacor</name>
</author>
<author><name sortKey="Buniel, Mc" uniqKey="Buniel M">MC Buniel</name>
</author>
<author><name sortKey="Chang, L" uniqKey="Chang L">L Chang</name>
</author>
<author><name sortKey="Fernandez, Sj" uniqKey="Fernandez S">SJ Fernandez</name>
</author>
<author><name sortKey="Gong, Y" uniqKey="Gong Y">Y Gong</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jucker, M" uniqKey="Jucker M">M Jucker</name>
</author>
<author><name sortKey="Walker, Lc" uniqKey="Walker L">LC Walker</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jucker, M" uniqKey="Jucker M">M Jucker</name>
</author>
<author><name sortKey="Walker, Lc" uniqKey="Walker L">LC Walker</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Meyer Luehmann, M" uniqKey="Meyer Luehmann M">M Meyer-Luehmann</name>
</author>
<author><name sortKey="Coomaraswamy, J" uniqKey="Coomaraswamy J">J Coomaraswamy</name>
</author>
<author><name sortKey="Bolmont, T" uniqKey="Bolmont T">T Bolmont</name>
</author>
<author><name sortKey="Kaeser, S" uniqKey="Kaeser S">S Kaeser</name>
</author>
<author><name sortKey="Schaefer, C" uniqKey="Schaefer C">C Schaefer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Eisele, Ys" uniqKey="Eisele Y">YS Eisele</name>
</author>
<author><name sortKey="Bolmont, T" uniqKey="Bolmont T">T Bolmont</name>
</author>
<author><name sortKey="Heikenwalder, M" uniqKey="Heikenwalder M">M Heikenwalder</name>
</author>
<author><name sortKey="Langer, F" uniqKey="Langer F">F Langer</name>
</author>
<author><name sortKey="Jacobson, Lh" uniqKey="Jacobson L">LH Jacobson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kane, Md" uniqKey="Kane M">MD Kane</name>
</author>
<author><name sortKey="Lipinski, Wj" uniqKey="Lipinski W">WJ Lipinski</name>
</author>
<author><name sortKey="Callahan, Mj" uniqKey="Callahan M">MJ Callahan</name>
</author>
<author><name sortKey="Bian, F" uniqKey="Bian F">F Bian</name>
</author>
<author><name sortKey="Durham, Ra" uniqKey="Durham R">RA Durham</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Watts, Jc" uniqKey="Watts J">JC Watts</name>
</author>
<author><name sortKey="Giles, K" uniqKey="Giles K">K Giles</name>
</author>
<author><name sortKey="Grillo, Sk" uniqKey="Grillo S">SK Grillo</name>
</author>
<author><name sortKey="Lemus, A" uniqKey="Lemus A">A Lemus</name>
</author>
<author><name sortKey="Dearmond, Sj" uniqKey="Dearmond S">SJ DeArmond</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Stohr, J" uniqKey="Stohr J">J Stohr</name>
</author>
<author><name sortKey="Watts, Jc" uniqKey="Watts J">JC Watts</name>
</author>
<author><name sortKey="Mensinger, Zl" uniqKey="Mensinger Z">ZL Mensinger</name>
</author>
<author><name sortKey="Oehler, A" uniqKey="Oehler A">A Oehler</name>
</author>
<author><name sortKey="Grillo, Sk" uniqKey="Grillo S">SK Grillo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Watts, Jc" uniqKey="Watts J">JC Watts</name>
</author>
<author><name sortKey="Condello, C" uniqKey="Condello C">C Condello</name>
</author>
<author><name sortKey="Stohr, J" uniqKey="Stohr J">J Stohr</name>
</author>
<author><name sortKey="Oehler, A" uniqKey="Oehler A">A Oehler</name>
</author>
<author><name sortKey="Lee, J" uniqKey="Lee J">J Lee</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Aguzzi, A" uniqKey="Aguzzi A">A Aguzzi</name>
</author>
<author><name sortKey="Rajendran, L" uniqKey="Rajendran L">L Rajendran</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Prusiner, Sb" uniqKey="Prusiner S">SB Prusiner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Olanow, Cw" uniqKey="Olanow C">CW Olanow</name>
</author>
<author><name sortKey="Brundin, P" uniqKey="Brundin P">P Brundin</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yagi, H" uniqKey="Yagi H">H Yagi</name>
</author>
<author><name sortKey="Kusaka, E" uniqKey="Kusaka E">E Kusaka</name>
</author>
<author><name sortKey="Hongo, K" uniqKey="Hongo K">K Hongo</name>
</author>
<author><name sortKey="Mizobata, T" uniqKey="Mizobata T">T Mizobata</name>
</author>
<author><name sortKey="Kawata, Y" uniqKey="Kawata Y">Y Kawata</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Prusiner, Sb" uniqKey="Prusiner S">SB Prusiner</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Griffith, Js" uniqKey="Griffith J">JS Griffith</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Desplats, P" uniqKey="Desplats P">P Desplats</name>
</author>
<author><name sortKey="Lee, Hj" uniqKey="Lee H">HJ Lee</name>
</author>
<author><name sortKey="Bae, Ej" uniqKey="Bae E">EJ Bae</name>
</author>
<author><name sortKey="Patrick, C" uniqKey="Patrick C">C Patrick</name>
</author>
<author><name sortKey="Rockenstein, E" uniqKey="Rockenstein E">E Rockenstein</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hansen, C" uniqKey="Hansen C">C Hansen</name>
</author>
<author><name sortKey="Angot, E" uniqKey="Angot E">E Angot</name>
</author>
<author><name sortKey="Bergstrom, Al" uniqKey="Bergstrom A">AL Bergstrom</name>
</author>
<author><name sortKey="Steiner, Ja" uniqKey="Steiner J">JA Steiner</name>
</author>
<author><name sortKey="Pieri, L" uniqKey="Pieri L">L Pieri</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chia, R" uniqKey="Chia R">R Chia</name>
</author>
<author><name sortKey="Tattum, Mh" uniqKey="Tattum M">MH Tattum</name>
</author>
<author><name sortKey="Jones, S" uniqKey="Jones S">S Jones</name>
</author>
<author><name sortKey="Collinge, J" uniqKey="Collinge J">J Collinge</name>
</author>
<author><name sortKey="Fisher, Em" uniqKey="Fisher E">EM Fisher</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Munch, C" uniqKey="Munch C">C Munch</name>
</author>
<author><name sortKey="O Rien, J" uniqKey="O Rien J">J O’Brien</name>
</author>
<author><name sortKey="Bertolotti, A" uniqKey="Bertolotti A">A Bertolotti</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Furukawa, Y" uniqKey="Furukawa Y">Y Furukawa</name>
</author>
<author><name sortKey="Kaneko, K" uniqKey="Kaneko K">K Kaneko</name>
</author>
<author><name sortKey="Watanabe, S" uniqKey="Watanabe S">S Watanabe</name>
</author>
<author><name sortKey="Yamanaka, K" uniqKey="Yamanaka K">K Yamanaka</name>
</author>
<author><name sortKey="Nukina, N" uniqKey="Nukina N">N Nukina</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kayed, R" uniqKey="Kayed R">R Kayed</name>
</author>
<author><name sortKey="Head, E" uniqKey="Head E">E Head</name>
</author>
<author><name sortKey="Sarsoza, F" uniqKey="Sarsoza F">F Sarsoza</name>
</author>
<author><name sortKey="Saing, T" uniqKey="Saing T">T Saing</name>
</author>
<author><name sortKey="Cotman, Cw" uniqKey="Cotman C">CW Cotman</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wu, Jw" uniqKey="Wu J">JW Wu</name>
</author>
<author><name sortKey="Breydo, L" uniqKey="Breydo L">L Breydo</name>
</author>
<author><name sortKey="Isas, Jm" uniqKey="Isas J">JM Isas</name>
</author>
<author><name sortKey="Lee, J" uniqKey="Lee J">J Lee</name>
</author>
<author><name sortKey="Kuznetsov, Yg" uniqKey="Kuznetsov Y">YG Kuznetsov</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kumar, A" uniqKey="Kumar A">A Kumar</name>
</author>
<author><name sortKey="Rice, Bl" uniqKey="Rice B">BL Rice</name>
</author>
<author><name sortKey="Patel, P" uniqKey="Patel P">P Patel</name>
</author>
<author><name sortKey="Paslay, Lc" uniqKey="Paslay L">LC Paslay</name>
</author>
<author><name sortKey="Singh, D" uniqKey="Singh D">D Singh</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kumar A, Pl" uniqKey="Kumar A P">PL Kumar A</name>
</author>
<author><name sortKey="Lyons, D" uniqKey="Lyons D">D Lyons</name>
</author>
<author><name sortKey="Morgan, Se" uniqKey="Morgan S">SE Morgan</name>
</author>
<author><name sortKey="Correia, Jj" uniqKey="Correia J">JJ Correia</name>
</author>
<author><name sortKey="Rangachari, V" uniqKey="Rangachari V">V Rangachari</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Barghorn, S" uniqKey="Barghorn S">S Barghorn</name>
</author>
<author><name sortKey="Nimmrich, V" uniqKey="Nimmrich V">V Nimmrich</name>
</author>
<author><name sortKey="Striebinger, A" uniqKey="Striebinger A">A Striebinger</name>
</author>
<author><name sortKey="Krantz, C" uniqKey="Krantz C">C Krantz</name>
</author>
<author><name sortKey="Keller, P" uniqKey="Keller P">P Keller</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shevchenko, A" uniqKey="Shevchenko A">A Shevchenko</name>
</author>
<author><name sortKey="Wilm, M" uniqKey="Wilm M">M Wilm</name>
</author>
<author><name sortKey="Vorm, O" uniqKey="Vorm O">O Vorm</name>
</author>
<author><name sortKey="Mann, M" uniqKey="Mann M">M Mann</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wong, He" uniqKey="Wong H">HE Wong</name>
</author>
<author><name sortKey="Irwin, Ja" uniqKey="Irwin J">JA Irwin</name>
</author>
<author><name sortKey="Kwon, I" uniqKey="Kwon I">I Kwon</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kukar, T" uniqKey="Kukar T">T Kukar</name>
</author>
<author><name sortKey="Murphy, Mp" uniqKey="Murphy M">MP Murphy</name>
</author>
<author><name sortKey="Eriksen, Jl" uniqKey="Eriksen J">JL Eriksen</name>
</author>
<author><name sortKey="Sagi, Sa" uniqKey="Sagi S">SA Sagi</name>
</author>
<author><name sortKey="Weggen, S" uniqKey="Weggen S">S Weggen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Yamamoto, Y" uniqKey="Yamamoto Y">Y Yamamoto</name>
</author>
<author><name sortKey="Gaynor, Rb" uniqKey="Gaynor R">RB Gaynor</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wilde, Gj" uniqKey="Wilde G">GJ Wilde</name>
</author>
<author><name sortKey="Pringle, Ak" uniqKey="Pringle A">AK Pringle</name>
</author>
<author><name sortKey="Sundstrom, Le" uniqKey="Sundstrom L">LE Sundstrom</name>
</author>
<author><name sortKey="Mann, Da" uniqKey="Mann D">DA Mann</name>
</author>
<author><name sortKey="Iannotti, F" uniqKey="Iannotti F">F Iannotti</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tamatani, M" uniqKey="Tamatani M">M Tamatani</name>
</author>
<author><name sortKey="Che, Yh" uniqKey="Che Y">YH Che</name>
</author>
<author><name sortKey="Matsuzaki, H" uniqKey="Matsuzaki H">H Matsuzaki</name>
</author>
<author><name sortKey="Ogawa, S" uniqKey="Ogawa S">S Ogawa</name>
</author>
<author><name sortKey="Okado, H" uniqKey="Okado H">H Okado</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Caughey, B" uniqKey="Caughey B">B Caughey</name>
</author>
<author><name sortKey="Kocisko, Da" uniqKey="Kocisko D">DA Kocisko</name>
</author>
<author><name sortKey="Raymond, Gj" uniqKey="Raymond G">GJ Raymond</name>
</author>
<author><name sortKey="Lansbury, Pt" uniqKey="Lansbury P">PT Lansbury</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jarrett, Jt" uniqKey="Jarrett J">JT Jarrett</name>
</author>
<author><name sortKey="Berger, Ep" uniqKey="Berger E">EP Berger</name>
</author>
<author><name sortKey="Lansbury, Pt" uniqKey="Lansbury P">PT Lansbury</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="O Uallain, B" uniqKey="O Uallain B">B O’Nuallain</name>
</author>
<author><name sortKey="Shivaprasad, S" uniqKey="Shivaprasad S">S Shivaprasad</name>
</author>
<author><name sortKey="Kheterpal, I" uniqKey="Kheterpal I">I Kheterpal</name>
</author>
<author><name sortKey="Wetzel, R" uniqKey="Wetzel R">R Wetzel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gonzalez Montalban, N" uniqKey="Gonzalez Montalban N">N Gonzalez-Montalban</name>
</author>
<author><name sortKey="Makarava, N" uniqKey="Makarava N">N Makarava</name>
</author>
<author><name sortKey="Ostapchenko, Vg" uniqKey="Ostapchenko V">VG Ostapchenko</name>
</author>
<author><name sortKey="Savtchenk, R" uniqKey="Savtchenk R">R Savtchenk</name>
</author>
<author><name sortKey="Alexeeva, I" uniqKey="Alexeeva I">I Alexeeva</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Castilla, J" uniqKey="Castilla J">J Castilla</name>
</author>
<author><name sortKey="Saa, P" uniqKey="Saa P">P Saa</name>
</author>
<author><name sortKey="Hetz, C" uniqKey="Hetz C">C Hetz</name>
</author>
<author><name sortKey="Soto, C" uniqKey="Soto C">C Soto</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gursky, O" uniqKey="Gursky O">O Gursky</name>
</author>
<author><name sortKey="Aleshkov, S" uniqKey="Aleshkov S">S Aleshkov</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gast, K" uniqKey="Gast K">K Gast</name>
</author>
<author><name sortKey="Modler, Aj" uniqKey="Modler A">AJ Modler</name>
</author>
<author><name sortKey="Damaschun, H" uniqKey="Damaschun H">H Damaschun</name>
</author>
<author><name sortKey="Krober, R" uniqKey="Krober R">R Krober</name>
</author>
<author><name sortKey="Lutsch, G" uniqKey="Lutsch G">G Lutsch</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nichols, Mr" uniqKey="Nichols M">MR Nichols</name>
</author>
<author><name sortKey="Moss, Ma" uniqKey="Moss M">MA Moss</name>
</author>
<author><name sortKey="Reed, Dk" uniqKey="Reed D">DK Reed</name>
</author>
<author><name sortKey="Lin, Wl" uniqKey="Lin W">WL Lin</name>
</author>
<author><name sortKey="Mukhopadhyay, R" uniqKey="Mukhopadhyay R">R Mukhopadhyay</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ghosh, P" uniqKey="Ghosh P">P Ghosh</name>
</author>
<author><name sortKey="Kumar, A" uniqKey="Kumar A">A Kumar</name>
</author>
<author><name sortKey="Datta, B" uniqKey="Datta B">B Datta</name>
</author>
<author><name sortKey="Rangachari, V" uniqKey="Rangachari V">V Rangachari</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chromy, Ba" uniqKey="Chromy B">BA Chromy</name>
</author>
<author><name sortKey="Nowak, Rj" uniqKey="Nowak R">RJ Nowak</name>
</author>
<author><name sortKey="Lambert, Mp" uniqKey="Lambert M">MP Lambert</name>
</author>
<author><name sortKey="Viola, Kl" uniqKey="Viola K">KL Viola</name>
</author>
<author><name sortKey="Chang, L" uniqKey="Chang L">L Chang</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gellermann, Gp" uniqKey="Gellermann G">GP Gellermann</name>
</author>
<author><name sortKey="Byrnes, H" uniqKey="Byrnes H">H Byrnes</name>
</author>
<author><name sortKey="Striebinger, A" uniqKey="Striebinger A">A Striebinger</name>
</author>
<author><name sortKey="Ullrich, K" uniqKey="Ullrich K">K Ullrich</name>
</author>
<author><name sortKey="Mueller, R" uniqKey="Mueller R">R Mueller</name>
</author>
</analytic>
</biblStruct>
</listBibl>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title-group><journal-title>PLoS ONE</journal-title>
</journal-title-group>
<issn pub-type="epub">1932-6203</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25365422</article-id>
<article-id pub-id-type="pmc">4218758</article-id>
<article-id pub-id-type="publisher-id">PONE-D-14-33267</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0111492</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v2"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Biochemistry</subject>
<subj-group><subject>Proteins</subject>
<subj-group><subject>Protein Aggregation</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group><subject>Neuroscience</subject>
<subj-group><subject>Molecular Neuroscience</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v2"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Mental Health and Psychiatry</subject>
<subj-group><subject>Dementia</subject>
<subj-group><subject>Alzheimer Disease</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group><subject>Neurology</subject>
<subj-group><subject>Brain Diseases</subject>
<subject>Neurodegenerative Diseases</subject>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Self-Propagative Replication of Aβ Oligomers Suggests Potential Transmissibility in Alzheimer Disease</article-title>
<alt-title alt-title-type="running-head">Self-Propagative Replication of Aβ Oligomers</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Kumar</surname>
<given-names>Amit</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pate</surname>
<given-names>Kayla M.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Moss</surname>
<given-names>Melissa A.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dean</surname>
<given-names>Dexter N.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rangachari</surname>
<given-names>Vijayaraghavan</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
<addr-line>Department of Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, United States of America</addr-line>
</aff>
<aff id="aff2"><label>2</label>
<addr-line>Department of Chemical Engineering, University of South Carolina, Columbia, United States of America</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Mason</surname>
<given-names>Jody M.</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1"><addr-line>University of Essex, United Kingdom</addr-line>
</aff>
<author-notes><corresp id="cor1">* E-mail: <email>Vijay.rangachari@usm.edu</email>
</corresp>
<fn fn-type="COI-statement"><p><bold>Competing Interests: </bold>
The authors have declared that no competing interests exist.</p>
</fn>
<fn fn-type="con"><p>Conceived and designed the experiments: VR MAM AK. Performed the experiments: AK KMP DND. Analyzed the data: AK VR KMP MAM. Contributed to the writing of the manuscript: AK MAM VR.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>3</day>
<month>11</month>
<year>2014</year>
</pub-date>
<volume>9</volume>
<issue>11</issue>
<elocation-id>e111492</elocation-id>
<history><date date-type="received"><day>24</day>
<month>7</month>
<year>2014</year>
</date>
<date date-type="accepted"><day>16</day>
<month>9</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>© 2014 Kumar et al</copyright-statement>
<copyright-year>2014</copyright-year>
<copyright-holder>Kumar et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p>
</license>
</permissions>
<abstract><p>The aggregation of amyloid-β (Aβ) peptide and its deposition in parts of the brain form the central processes in the etiology of Alzheimer disease (AD). The low-molecular weight oligomers of Aβ aggregates (2 to 30 mers) are known to be the primary neurotoxic agents whose mechanisms of cellular toxicity and synaptic dysfunction have received substantial attention in the recent years. However, how these toxic agents proliferate and induce widespread amyloid deposition throughout the brain, and what mechanism is involved in the amplification and propagation of toxic oligomer species, are far from clear. Emerging evidence based on transgenic mice models indicates a transmissible nature of Aβ aggregates and implicates a prion-like mechanism of oligomer propagation, which manifests as the dissemination and proliferation of Aβ toxicity. Despite accumulating evidence in support of a transmissible nature of Aβ aggregates, a clear, molecular-level understanding of this intriguing mechanism is lacking. Recently, we reported the characterization of unique replicating oligomers of Aβ42 (12–24 mers) <italic>in</italic>
<italic>vitro</italic>
called <underline>L</underline>
arge <underline>F</underline>
atty <underline>A</underline>
cid-derived <underline>O</underline>
ligomers (LFAOs) (Kumar et al., 2012, <italic>J. Biol. Chem</italic>
). In the current report, we establish that LFAOs possess physiological activity by activating NF-κB in human neuroblastoma cells, and determine the experimental parameters that control the efficiency of LFAO replication by self-propagation. These findings constitute the first detailed report on monomer – oligomer lateral propagation reactions that may constitute potential mechanism governing transmissibility among Aβ oligomers. These data support the previous reports on transmissible mechanisms observed in transgenic animal models.</p>
</abstract>
<funding-group><funding-statement>This work was partly funded by National Center for Research Resources (5P20RR016476-11) and the National Institute of General Medical Sciences (8 P20 GM103476-11) from the National Institutes of Health for funding through INBRE (to VR), National Institutes of Health, National Institute of General Medical Sciences for funding through COBRE (P20GM103641) (to MAM), and American Heart Association (10GRNT4190124) (to VR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts><page-count count="11"></page-count>
</counts>
<custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name>
<meta-value>The authors confirm that all data underlying the findings are fully available without restriction. Data are available from Figshare using the DOI <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.6084/m9.figshare.1189297">http://dx.doi.org/10.6084/m9.figshare.1189297</ext-link>
.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes><title>Data Availability</title>
<p>The authors confirm that all data underlying the findings are fully available without restriction. Data are available from Figshare using the DOI <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.6084/m9.figshare.1189297">http://dx.doi.org/10.6084/m9.figshare.1189297</ext-link>
.</p>
</notes>
</front>
</pmc>
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