The interwoven fibril-like structure of amyloid-beta plaques in mouse brain tissue visualized using super-resolution STED microscopy.

Alzheimer’s disease Amyloid beta peptide Amyloid fibrils Immunohistochemistry Next generation drug design Super-resolution STED microscopy

Journal

Cell & bioscience
ISSN: 2045-3701
Titre abrégé: Cell Biosci
Pays: England
ID NLM: 101561195

Informations de publication

Date de publication:
04 Aug 2023
Historique:
received: 01 05 2023
accepted: 14 07 2023
medline: 5 8 2023
pubmed: 5 8 2023
entrez: 4 8 2023
Statut: epublish

Résumé

Standard neuropathologic analysis of Alzheimer's brain relies on traditional fluorescence microscopy, which suffers from limited spatial resolution due to light diffraction. As a result, it fails to reveal intricate details of amyloid plaques. While electron microscopy (EM) offers higher resolution, its extensive sample preparation, involving fixation, dehydration, embedding, and sectioning, can introduce artifacts and distortions in the complex brain tissue. Moreover, EM lacks molecular specificity and has limited field of view and imaging depth. In our study, we employed super-resolution Stimulated Emission Depletion (STED) microscopy in conjunction with the anti-human APP recombinant antibody 1C3 fluorescently labelled with DyLight The utilization of STED microscopy represents a groundbreaking advancement in the field, enabling researchers to delve into the characterization of local mechanisms that underlie Amyloid (Aβ) deposition into plaques and their subsequent clearance. This unprecedented level of detail is especially crucial for comprehending the etiology of Alzheimer's disease and developing the next generation of anti-amyloid treatments. By facilitating the evaluation of drug candidates and non-pharmacological interventions aiming to reduce amyloid burden, STED microscopy emerges as an indispensable tool for driving scientific progress in Alzheimer's research.

Sections du résumé

BACKGROUND BACKGROUND
Standard neuropathologic analysis of Alzheimer's brain relies on traditional fluorescence microscopy, which suffers from limited spatial resolution due to light diffraction. As a result, it fails to reveal intricate details of amyloid plaques. While electron microscopy (EM) offers higher resolution, its extensive sample preparation, involving fixation, dehydration, embedding, and sectioning, can introduce artifacts and distortions in the complex brain tissue. Moreover, EM lacks molecular specificity and has limited field of view and imaging depth.
RESULTS RESULTS
In our study, we employed super-resolution Stimulated Emission Depletion (STED) microscopy in conjunction with the anti-human APP recombinant antibody 1C3 fluorescently labelled with DyLight
CONCLUSIONS CONCLUSIONS
The utilization of STED microscopy represents a groundbreaking advancement in the field, enabling researchers to delve into the characterization of local mechanisms that underlie Amyloid (Aβ) deposition into plaques and their subsequent clearance. This unprecedented level of detail is especially crucial for comprehending the etiology of Alzheimer's disease and developing the next generation of anti-amyloid treatments. By facilitating the evaluation of drug candidates and non-pharmacological interventions aiming to reduce amyloid burden, STED microscopy emerges as an indispensable tool for driving scientific progress in Alzheimer's research.

Identifiants

pubmed: 37542303
doi: 10.1186/s13578-023-01086-4
pii: 10.1186/s13578-023-01086-4
pmc: PMC10403925
doi:

Types de publication

Journal Article

Langues

eng

Pagination

142

Subventions

Organisme : Vetenskapsrådet
ID : 2018-05337
Organisme : Vetenskapsrådet
ID : 2022-03402
Organisme : Stiftelsen Olle Engkvist Byggmästare
ID : 199-0480
Organisme : Magnus Bergvalls Stiftelse
ID : 2021-04376
Organisme : UAB-GE-26408
ID : UAB-GE-26408
Organisme : HORIZON EUROPE Reforming and enhancing the European Research and Innovation system
ID : No. 737390

Informations de copyright

© 2023. Society of Chinese Bioscientists in America (SCBA).

Références

Nat Commun. 2016 Jun 17;7:11915
pubmed: 27312972
Neurodegeneration. 1996 Mar;5(1):35-41
pubmed: 8731380
J Neurochem. 2007 Oct;103(1):334-45
pubmed: 17623042
Nanoscale. 2020 Jul 23;12(28):15050-15053
pubmed: 32666991
EBioMedicine. 2019 Apr;42:174-187
pubmed: 30926423
J Comp Neurol. 2019 Apr 1;527(5):985-998
pubmed: 30408165
Nat Med. 1997 Sep;3(9):1016-20
pubmed: 9288729
Acta Neuropathol. 2008 May;115(5):533-46
pubmed: 18343933
Neurotherapeutics. 2023 Jan;20(1):195-206
pubmed: 36253511
Annu Rev Neurosci. 2011;34:185-204
pubmed: 21456963
Mol Brain. 2021 Oct 13;14(1):158
pubmed: 34645511
Histopathology. 2001 Feb;38(2):120-34
pubmed: 11207825
Biomed Opt Express. 2020 Jan 08;11(2):660-671
pubmed: 32206391
Neuron. 2020 Jan 22;105(2):260-275.e6
pubmed: 31759806
Structure. 2005 Sep;13(9):1279-88
pubmed: 16154085
Biochemistry (Mosc). 2014 Dec;79(13):1515-27
pubmed: 25749162
J Am Chem Soc. 2000 Jun 7;122(22):5262-77
pubmed: 22339465
Science. 2002 Jul 19;297(5580):353-6
pubmed: 12130773
Nat Methods. 2018 Mar;15(3):173-182
pubmed: 29377014
J Mol Biol. 1996 Mar 15;256(5):870-7
pubmed: 8601838
Adv Exp Med Biol. 2019;1184:305-325
pubmed: 32096046
J Biol Chem. 1994 Dec 9;269(49):30773-6
pubmed: 7983005
J Theor Biol. 2020 Feb 7;486:110102
pubmed: 31809717
Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):13018-13023
pubmed: 29158413
J Alzheimers Dis. 2015;46(4):1007-20
pubmed: 25881910
Nat Struct Mol Biol. 2020 Dec;27(12):1125-1133
pubmed: 32989305
Q Rev Biophys. 2016 Jan;49:e2
pubmed: 26350150
N Engl J Med. 2023 Jan 5;388(1):9-21
pubmed: 36449413
Chin Med Sci J. 2018 Sep 20;33(3):167-173
pubmed: 30266107
Sci Rep. 2019 Mar 26;9(1):5181
pubmed: 30914681
Science. 2022 Jan 14;375(6577):167-172
pubmed: 35025654
EMBO J. 1999 Feb 15;18(4):815-21
pubmed: 10022824
J Negat Results Biomed. 2017 Jan 26;16(1):1
pubmed: 28126004
Am J Pathol. 2000 Jan;156(1):15-20
pubmed: 10623648
Lancet. 2000 Jan 1;355(9197):42-3
pubmed: 10615894
J Neurol Sci. 2018 Nov 15;394:99-106
pubmed: 30243104
Life (Basel). 2021 May 11;11(5):
pubmed: 34064766
Microsc Res Tech. 2005 Jul;67(3-4):210-7
pubmed: 16103997
Nature. 2022 May;605(7909):310-314
pubmed: 35344985
Front Mol Neurosci. 2019 Oct 02;12:233
pubmed: 31632238
J Mol Biol. 2000 Mar 31;297(3):569-83
pubmed: 10731412
J Neurosci. 2019 Nov 27;39(48):9623-9632
pubmed: 31658988
Am J Pathol. 2005 Aug;167(2):527-43
pubmed: 16049337
Cereb Cortex. 2019 Sep 13;29(10):4291-4302
pubmed: 30566579
J Alzheimers Dis. 2021;83(2):833-852
pubmed: 34366358
Acta Neuropathol Commun. 2016 Mar 31;4:29
pubmed: 27036709
Neuron. 2003 Jul 31;39(3):409-21
pubmed: 12895417

Auteurs

Björn Johansson (B)

Department of Clinical Neuroscience, Karolinska Institutet, SE-17176, Stockholm, Sweden.
Theme Aging, Karolinska University Hospital, Karolinska Institutet, SE-17176, Stockholm, Sweden.

Sho Oasa (S)

Department of Clinical Neuroscience, Karolinska Institutet, SE-17176, Stockholm, Sweden.

Aida Muntsant Soria (A)

Institut de Neurociències, Universitat Autònoma de Barcelona, 08193, Barcelona, Spain.
Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, 08193, Barcelona, Spain.

Ann Tiiman (A)

Department of Clinical Neuroscience, Karolinska Institutet, SE-17176, Stockholm, Sweden.

Linda Söderberg (L)

BioArctic AB, Stockholm, Sweden.

Ebba Amandius (E)

BioArctic AB, Stockholm, Sweden.

Christer Möller (C)

BioArctic AB, Stockholm, Sweden.

Lars Lannfelt (L)

BioArctic AB, Stockholm, Sweden.

Lars Terenius (L)

Department of Clinical Neuroscience, Karolinska Institutet, SE-17176, Stockholm, Sweden.

Lydia Giménez-Llort (L)

Institut de Neurociències, Universitat Autònoma de Barcelona, 08193, Barcelona, Spain.
Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, 08193, Barcelona, Spain.

Vladana Vukojević (V)

Department of Clinical Neuroscience, Karolinska Institutet, SE-17176, Stockholm, Sweden. vladana.vukojevic@ki.se.

Classifications MeSH