Structural differences in amyloid-β fibrils from brains of nondemented elderly individuals and Alzheimer's disease patients.
Alzheimer’s disease
amyloid structure
solid-state NMR
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
09 11 2021
09 11 2021
Historique:
received:
27
06
2021
accepted:
20
09
2021
entrez:
2
11
2021
pubmed:
3
11
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
Although amyloid plaques composed of fibrillar amyloid-β (Aβ) assemblies are a diagnostic hallmark of Alzheimer's disease (AD), quantities of amyloid similar to those in AD patients are observed in brain tissue of some nondemented elderly individuals. The relationship between amyloid deposition and neurodegeneration in AD has, therefore, been unclear. Here, we use solid-state NMR to investigate whether molecular structures of Aβ fibrils from brain tissue of nondemented elderly individuals with high amyloid loads differ from structures of Aβ fibrils from AD tissue. Two-dimensional solid-state NMR spectra of isotopically labeled Aβ fibrils, prepared by seeded growth from frontal lobe tissue extracts, are similar in the two cases but with statistically significant differences in intensity distributions of cross-peak signals. Differences in solid-state NMR data are greater for 42-residue amyloid-β (Aβ42) fibrils than for 40-residue amyloid-β (Aβ40) fibrils. These data suggest that similar sets of fibril polymorphs develop in nondemented elderly individuals and AD patients but with different relative populations on average.
Identifiants
pubmed: 34725161
pii: 2111863118
doi: 10.1073/pnas.2111863118
pmc: PMC8609303
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MC_UP_1604/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00024/8
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : Z01 DK029061
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing interest.
Références
Arch Neurol. 2008 Nov;65(11):1509-17
pubmed: 19001171
Science. 2017 Oct 6;358(6359):116-119
pubmed: 28882996
Neuron. 2014 Jun 18;82(6):1271-88
pubmed: 24857020
PLoS One. 2015 Jul 29;10(7):e0123743
pubmed: 26221954
Nat Commun. 2019 Oct 29;10(1):4760
pubmed: 31664019
Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):10323-8
pubmed: 24982139
Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):E782-E791
pubmed: 29311311
Ann Neurol. 2013 Jun;73(6):751-61
pubmed: 23596051
Biol Psychiatry. 2018 Feb 15;83(4):358-368
pubmed: 29331212
J Am Chem Soc. 2016 Aug 3;138(30):9663-74
pubmed: 27355699
Nature. 2018 Sep;561(7721):137-140
pubmed: 30158706
Neuropsychologia. 2008;46(6):1688-97
pubmed: 18343463
Nature. 2017 Jul 13;547(7662):185-190
pubmed: 28678775
Sci Rep. 2020 Mar 31;10(1):5720
pubmed: 32235842
Nat Struct Mol Biol. 2015 Jun;22(6):499-505
pubmed: 25938662
EMBO Mol Med. 2016 Jun 01;8(6):595-608
pubmed: 27025652
Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):10329-34
pubmed: 24982137
Cell. 2013 Jul 3;154(1):103-17
pubmed: 23827677
J Biol Chem. 2016 Jun 3;291(23):12233-44
pubmed: 27056326
Neurodegener Dis. 2010;7(1-3):38-41
pubmed: 20160456
Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):409-414
pubmed: 29279394
Neurobiol Aging. 1996 Nov-Dec;17(6):921-33
pubmed: 9363804
J Biol Chem. 2016 Feb 12;291(7):3174-83
pubmed: 26719327
Alzheimers Dement. 2014 Oct;10(5 Suppl):S344-53
pubmed: 24418052
Nat Neurosci. 2020 Oct;23(10):1183-1193
pubmed: 32778792
Nat Med. 1998 Oct;4(10):1157-65
pubmed: 9771749
Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):E4976-84
pubmed: 27469165
JAMA. 2000 Mar 22-29;283(12):1571-7
pubmed: 10735393
Trends Cogn Sci. 2013 Oct;17(10):502-9
pubmed: 24018144
Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):13018-13023
pubmed: 29158413
Protein Sci. 2018 Jul;27(7):1218-1230
pubmed: 29417648
Curr Opin Chem Biol. 2012 Apr;16(1-2):67-73
pubmed: 22366383
J Am Chem Soc. 2016 Aug 10;138(31):9840-52
pubmed: 27414264
Nat Struct Mol Biol. 2016 May;23(5):409-15
pubmed: 27018801
Nat Commun. 2018 Sep 6;9(1):3609
pubmed: 30190461
Science. 2006 Sep 22;313(5794):1781-4
pubmed: 16990547
Chem Commun (Camb). 2018 May 15;54(40):5070-5073
pubmed: 29707712
J Alzheimers Dis. 2018;64(s1):S161-S189
pubmed: 29865057
Curr Alzheimer Res. 2007 Apr;4(2):191-7
pubmed: 17430246
Nature. 2016 Nov 09;539(7628):217-226
pubmed: 27830781
Proc Natl Acad Sci U S A. 2021 Jan 26;118(4):
pubmed: 33431654
Neuron. 2015 May 6;86(3):632-45
pubmed: 25950632
Brain. 2009 May;132(Pt 5):1355-65
pubmed: 19339253
Cell. 2017 Oct 19;171(3):615-627.e16
pubmed: 28942918
Protein Expr Purif. 2006 Jul;48(1):112-7
pubmed: 16564705
Biochemistry. 2007 Nov 27;46(47):13505-22
pubmed: 17979302
J Mol Biol. 2005 Sep 16;352(2):282-98
pubmed: 16095615
Proc Natl Acad Sci U S A. 2009 May 5;106(18):7443-8
pubmed: 19376973
Brain Res Brain Res Rev. 1997 Oct;25(2):217-45
pubmed: 9403139
N Engl J Med. 2009 May 28;360(22):2302-9
pubmed: 19474427
J Biol Chem. 1998 Nov 27;273(48):32230-5
pubmed: 9822701
Nature. 2020 Sep;585(7825):464-469
pubmed: 32461689
Nature. 2020 Apr;580(7802):283-287
pubmed: 32050258
J Am Chem Soc. 2011 Mar 23;133(11):4018-29
pubmed: 21355554
Science. 2005 Jan 14;307(5707):262-5
pubmed: 15653506
Nature. 2017 Jan 12;541(7636):217-221
pubmed: 28052060
Alzheimers Res Ther. 2017 Aug 9;9(1):60
pubmed: 28793924
Nature. 2019 Apr;568(7752):420-423
pubmed: 30894745
Cell. 2013 Sep 12;154(6):1257-68
pubmed: 24034249