Skip to main content
Top
Published in: Acta Neuropathologica 3/2014

Open Access 01-09-2014 | Correspondence

Inside Alzheimer brain with CLARITY: senile plaques, neurofibrillary tangles and axons in 3-D

Authors: Kunie Ando, Quentin Laborde, Adina Lazar, David Godefroy, Ihsen Youssef, Majid Amar, Amy Pooler, Marie-Claude Potier, Benoit Delatour, Charles Duyckaerts

Published in: Acta Neuropathologica | Issue 3/2014

Login to get access

Excerpt

Alzheimer’s disease (AD) is characterized by extracellular deposits of amyloid β (Aβ) peptide and intracellular tau aggregates. Examination of these lesions in post-mortem brain tissue routinely provides a two-dimensional picture of the pathology with a limited depth of field. Several tissue-clearing protocols have been recently published [1, 46, 8, 10, 11, 16]. We compared the quality of immunostaining on post-mortem human brain tissues using several clearing techniques including CLARITY [4, 5], Scale [8], SeeDB [9], and 3DISCO [6]. Results were best with CLARITY. In that method, acrylamide hydrogel links the protein of the tissue and maintains its structure. Removing the lipids makes the block transparent and facilitates antibody diffusion [4, 5]. We noticed that the results were improved if ScaleA2 [8] was used to mount the block after CLARITY. …
Appendix
Available only for authorised users
Literature
2.
go back to reference Braak E, Braak H, Mandelkow EM (1994) A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol 87:554–567PubMedCrossRef Braak E, Braak H, Mandelkow EM (1994) A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol 87:554–567PubMedCrossRef
3.
go back to reference Brion JP, Hanger DP, Bruce MT, Couck AM, Flament-Durand J, Anderton BH (1991) Tau in Alzheimer neurofibrillary tangles. N- and C-terminal regions are differentially associated with paired helical filaments and the location of a putative abnormal phosphorylation site. Biochem J 273(Pt 1):127–133PubMedCentralPubMed Brion JP, Hanger DP, Bruce MT, Couck AM, Flament-Durand J, Anderton BH (1991) Tau in Alzheimer neurofibrillary tangles. N- and C-terminal regions are differentially associated with paired helical filaments and the location of a putative abnormal phosphorylation site. Biochem J 273(Pt 1):127–133PubMedCentralPubMed
4.
6.
go back to reference Erturk A, Becker K, Jahrling N et al (2012) Three-dimensional imaging of solvent-cleared organs using 3DISCO. Nat Protoc 7:1983–1995PubMedCrossRef Erturk A, Becker K, Jahrling N et al (2012) Three-dimensional imaging of solvent-cleared organs using 3DISCO. Nat Protoc 7:1983–1995PubMedCrossRef
7.
go back to reference Garcia-Alloza M, Borrelli LA, Rozkalne A, Hyman BT, Bacskai BJ (2007) Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. J Neurochem 102:1095–1104PubMedCrossRef Garcia-Alloza M, Borrelli LA, Rozkalne A, Hyman BT, Bacskai BJ (2007) Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. J Neurochem 102:1095–1104PubMedCrossRef
8.
go back to reference Hama H, Kurokawa H, Kawano H et al (2011) Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain. Nat Neurosci 14:1481–1488PubMedCrossRef Hama H, Kurokawa H, Kawano H et al (2011) Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain. Nat Neurosci 14:1481–1488PubMedCrossRef
9.
go back to reference Ke MT, Fujimoto S, Imai T (2013) SeeDB: a simple and morphology-preserving optical clearing agent for neuronal circuit reconstruction. Nat Neurosci 16:1154–1161PubMedCrossRef Ke MT, Fujimoto S, Imai T (2013) SeeDB: a simple and morphology-preserving optical clearing agent for neuronal circuit reconstruction. Nat Neurosci 16:1154–1161PubMedCrossRef
10.
go back to reference Knowles RB, Wyart C, Buldyrev SV et al (1999) Plaque-induced neurite abnormalities: implications for disruption of neural networks in Alzheimer’s disease. Proc Natl Acad Sci USA 96:5274–5279PubMedCentralPubMedCrossRef Knowles RB, Wyart C, Buldyrev SV et al (1999) Plaque-induced neurite abnormalities: implications for disruption of neural networks in Alzheimer’s disease. Proc Natl Acad Sci USA 96:5274–5279PubMedCentralPubMedCrossRef
11.
go back to reference Kuwajima T, Sitko AA, Bhansali P, Jurgens C, Guido W, Mason C (2013) ClearT: a detergent- and solvent-free clearing method for neuronal and non-neuronal tissue. Development 140:1364–1368PubMedCentralPubMedCrossRef Kuwajima T, Sitko AA, Bhansali P, Jurgens C, Guido W, Mason C (2013) ClearT: a detergent- and solvent-free clearing method for neuronal and non-neuronal tissue. Development 140:1364–1368PubMedCentralPubMedCrossRef
12.
go back to reference Le R, Cruz L, Urbanc B et al (2001) Plaque-induced abnormalities in neurite geometry in transgenic models of Alzheimer disease: implications for neural system disruption. J Neuropathol Exp Neurol 60:753–758PubMed Le R, Cruz L, Urbanc B et al (2001) Plaque-induced abnormalities in neurite geometry in transgenic models of Alzheimer disease: implications for neural system disruption. J Neuropathol Exp Neurol 60:753–758PubMed
13.
go back to reference Meyer-Luehmann M, Spires-Jones TL, Prada C et al (2008) Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease. Nature 451:720–724PubMedCentralPubMedCrossRef Meyer-Luehmann M, Spires-Jones TL, Prada C et al (2008) Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease. Nature 451:720–724PubMedCentralPubMedCrossRef
14.
go back to reference Serrano-Pozo A, William CM, Ferrer I et al (2010) Beneficial effect of human anti-amyloid-beta active immunization on neurite morphology and tau pathology. Brain 133:1312–1327PubMedCentralPubMedCrossRef Serrano-Pozo A, William CM, Ferrer I et al (2010) Beneficial effect of human anti-amyloid-beta active immunization on neurite morphology and tau pathology. Brain 133:1312–1327PubMedCentralPubMedCrossRef
15.
go back to reference Spires TL, Meyer-Luehmann M, Stern EA et al (2005) Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J Neurosci 25:7278–7287PubMedCentralPubMedCrossRef Spires TL, Meyer-Luehmann M, Stern EA et al (2005) Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J Neurosci 25:7278–7287PubMedCentralPubMedCrossRef
16.
go back to reference Susaki EA, Tainaka K, Perrin D et al (2014) Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis. Cell 157:726–739PubMedCrossRef Susaki EA, Tainaka K, Perrin D et al (2014) Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis. Cell 157:726–739PubMedCrossRef
Metadata
Title
Inside Alzheimer brain with CLARITY: senile plaques, neurofibrillary tangles and axons in 3-D
Authors
Kunie Ando
Quentin Laborde
Adina Lazar
David Godefroy
Ihsen Youssef
Majid Amar
Amy Pooler
Marie-Claude Potier
Benoit Delatour
Charles Duyckaerts
Publication date
01-09-2014
Publisher
Springer Berlin Heidelberg
Published in
Acta Neuropathologica / Issue 3/2014
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-014-1322-y

Other articles of this Issue 3/2014

Acta Neuropathologica 3/2014 Go to the issue