title: Amyloid Beta annular protofibrils in cell processes and synapses accumulate with aging and Alzheimer-associated genetic modification.
abstract: Amyloid beta (Abeta) annular protofibrils (APFs) have been described where the structure is related to that of beta barrel pore-forming bacterial toxins and exhibits cellular toxicity. To investigate the relationship of Abeta APFs to disease and their ultrastructural localization in brain tissue, we conducted a pre-embedding immunoelectron microscopic study using anti-annular protofibril antiserum. We examined brain tissues of young- and old-aged amyloid precursor protein transgenic mice (APP23), neprilysin knockout APP23 mice, and nontransgenic littermates. alphaAPF-immunoreactions tended to be found (1) on plasma membranes and vesicles inside of cell processes, but not on amyloid fibrils, (2) with higher density due to aging, APP transgene, and neprilysin deficiency, and (3) with higher positive rate at synaptic compartments in aged APP23, especially in neprilysin knockout APP23 mice. These findings imply that APFs are distinct from amyloid fibrils, interact with biological membranes, and might be related to synaptic dysfunction in Alzheimer model mouse brains.
authors.affiliation: School of Health Sciences, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8514, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Kokubo
authors.forename: Rakez
authors.initials: R
authors.lastname: Kayed
authors.forename: Charles G
authors.initials: CG
authors.lastname: Glabe
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: Takaomi C
authors.initials: TC
authors.lastname: Saido
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Iwata
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Yamaguchi
references.citation: J Neurosci. 2004 Jan 28;24(4):991-8
references.pmid: 14749444
references.citation: J Neurosci. 1998 Dec 1;18(23):9629-37
references.pmid: 9822724
references.citation: Biochim Biophys Acta. 2007 May;1768(5):1128-37
references.pmid: 17306220
references.citation: Nature. 2006 Mar 16;440(7082):352-7
references.pmid: 16541076
references.citation: J Neurosci. 2004 Apr 7;24(14):3592-9
references.pmid: 15071107
references.citation: Biochemistry. 2003 Nov 11;42(44):12749-60
references.pmid: 14596589
references.citation: Nat Neurosci. 2005 Aug;8(8):1051-8
references.pmid: 16025111
references.citation: Neurobiol Aging. 2006 Apr;27(4):570-5
references.pmid: 16481071
references.citation: Ann Neurol. 1999 Dec;46(6):860-6
references.pmid: 10589538
references.citation: J Neurosci. 2004 Nov 10;24(45):10191-200
references.pmid: 15537891
references.citation: Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13287-92
references.pmid: 9371838
references.citation: Nat Neurosci. 2001 Sep;4(9):887-93
references.pmid: 11528419
references.citation: Proc Natl Acad Sci U S A. 1998 May 26;95(11):6448-53
references.pmid: 9600986
references.citation: Science. 2002 Oct 25;298(5594):789-91
references.pmid: 12399581
references.citation: Brain Res. 2005 May 31;1045(1-2):224-8
references.pmid: 15910781
references.citation: Nature. 2002 Apr 4;416(6880):535-9
references.pmid: 11932745
references.citation: Neuromolecular Med. 2007;9(3):270-5
references.pmid: 17914185
references.citation: Exp Neurol. 1999 Aug;158(2):328-37
references.pmid: 10415140
references.citation: Nat Rev Mol Cell Biol. 2007 Feb;8(2):101-12
references.pmid: 17245412
references.citation: Am J Pathol. 1999 Sep;155(3):853-62
references.pmid: 10487842
references.citation: Neurosci Lett. 2001 Jan 12;297(2):97-100
references.pmid: 11121879
references.citation: J Biol Chem. 2009 Feb 13;284(7):4230-7
references.pmid: 19098006
references.citation: Curr Opin Struct Biol. 2000 Feb;10(1):60-8
references.pmid: 10679462
references.citation: Science. 2003 Apr 18;300(5618):486-9
references.pmid: 12702875
references.citation: Brain Res. 2005 Jan 21;1031(2):222-8
references.pmid: 15649447
references.citation: Biochim Biophys Acta. 2007 Aug;1768(8):1966-75
references.pmid: 17553456
references.citation: J Biol Chem. 2004 Nov 5;279(45):46363-6
references.pmid: 15385542
references.citation: J Biol Chem. 2006 Jun 30;281(26):17941-51
references.pmid: 16636059
references.citation: J Neuropathol Exp Neurol. 2000 Aug;59(8):723-32
references.pmid: 10952062
references.citation: Biochemistry. 2000 Sep 5;39(35):10831-9
references.pmid: 10978169
references.citation: J Neurosci. 2007 Jan 24;27(4):796-807
references.pmid: 17251419
references.citation: Biochem Biophys Res Commun. 2003 Oct 10;310(1):236-41
references.pmid: 14511676
references.citation: Ann N Y Acad Sci. 2003 Nov;1003:1-11
references.pmid: 14684431
references.citation: Brain Res. 2003 Mar 7;965(1-2):83-90
references.pmid: 12591123
references.citation: J Neurosci. 2002 Nov 15;22(22):9785-93
references.pmid: 12427834
references.citation: Nature. 2002 Jul 18;418(6895):291
references.pmid: 12124613