Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer’s disease brains: Implications for in-vivo diagnostics

Abstract The combined fluorescent and Aβ-binding properties of the dietary spice curcumin could yield diagnostic purpose in the search for a non-invasive Aβ-biomarker for Alzheimer’s disease (AD). However, evidence on the binding properties of curcumin, its conjugates and clinically used bio-availab...

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Main Authors: Jurre den Haan, Tjado H. J. Morrema, Annemieke J. Rozemuller, Femke H. Bouwman, Jeroen J. M. Hoozemans
Format: Article
Language:English
Published: BMC 2018-08-01
Series:Acta Neuropathologica Communications
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40478-018-0577-2
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author Jurre den Haan
Tjado H. J. Morrema
Annemieke J. Rozemuller
Femke H. Bouwman
Jeroen J. M. Hoozemans
author_facet Jurre den Haan
Tjado H. J. Morrema
Annemieke J. Rozemuller
Femke H. Bouwman
Jeroen J. M. Hoozemans
author_sort Jurre den Haan
collection DOAJ
description Abstract The combined fluorescent and Aβ-binding properties of the dietary spice curcumin could yield diagnostic purpose in the search for a non-invasive Aβ-biomarker for Alzheimer’s disease (AD). However, evidence on the binding properties of curcumin, its conjugates and clinically used bio-available formulations to AD neuropathological hallmarks is scarce. We therefore assessed the binding properties of different curcumin forms to different neuropathological deposits in post-mortem brain tissue of cases with AD, other neurodegenerative diseases, and controls. Post mortem brain tissue was histochemically assessed for the binding of curcumin, its isoforms, conjugates and bio-available forms and compared to routinely used staining methods. For this study we included brains of early onset AD, late onset AD, primary age-related tauopathy (PART), cerebral amyloid angiopathy (CAA), frontotemporal lobar degeneration (FTLD) with tau or TAR DNA-binding protein 43 (TDP-43) inclusions, dementia with Lewy bodies (DLB), Parkinson’s disease (PD) and control cases without brain pathology. We found that curcumin binds to fibrillar amyloid beta (Aβ) in plaques and CAA. It does not specifically bind to inclusions of protein aggregates in FTLD-tau cases, TDP-43, or Lewy bodies. Curcumin isoforms, conjugates and bio-available forms show affinity for the same Aβ structures. Curcumin staining overlaps with immunohistochemical detection of Aβ in fibrillar plaques and CAA, and to a lesser extent cored plaques. A weak staining of neurofibrillary tangles was observed, while other structures immunopositive for phosphorylated tau remained negative. In conclusion, curcumin, its isoforms, conjugates and bio-available forms selectively bind fibrillar Aβ in plaques and CAA in post mortem AD brain tissue. Curcumin, being a food additive with fluorescent properties, is therefore an interesting candidate for in-vivo diagnostics in AD, for example in retinal fluorescent imaging.
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spelling doaj.art-75dd0001f4e54955828b760001c44bea2022-12-22T03:58:12ZengBMCActa Neuropathologica Communications2051-59602018-08-016111210.1186/s40478-018-0577-2Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer’s disease brains: Implications for in-vivo diagnosticsJurre den Haan0Tjado H. J. Morrema1Annemieke J. Rozemuller2Femke H. Bouwman3Jeroen J. M. Hoozemans4Department of Neurology, Amsterdam Neuroscience, VU University Medical Center Alzheimer CenterDepartment of Pathology, Amsterdam Neuroscience, VU University Medical CenterDepartment of Pathology, Amsterdam Neuroscience, VU University Medical CenterDepartment of Neurology, Amsterdam Neuroscience, VU University Medical Center Alzheimer CenterDepartment of Pathology, Amsterdam Neuroscience, VU University Medical CenterAbstract The combined fluorescent and Aβ-binding properties of the dietary spice curcumin could yield diagnostic purpose in the search for a non-invasive Aβ-biomarker for Alzheimer’s disease (AD). However, evidence on the binding properties of curcumin, its conjugates and clinically used bio-available formulations to AD neuropathological hallmarks is scarce. We therefore assessed the binding properties of different curcumin forms to different neuropathological deposits in post-mortem brain tissue of cases with AD, other neurodegenerative diseases, and controls. Post mortem brain tissue was histochemically assessed for the binding of curcumin, its isoforms, conjugates and bio-available forms and compared to routinely used staining methods. For this study we included brains of early onset AD, late onset AD, primary age-related tauopathy (PART), cerebral amyloid angiopathy (CAA), frontotemporal lobar degeneration (FTLD) with tau or TAR DNA-binding protein 43 (TDP-43) inclusions, dementia with Lewy bodies (DLB), Parkinson’s disease (PD) and control cases without brain pathology. We found that curcumin binds to fibrillar amyloid beta (Aβ) in plaques and CAA. It does not specifically bind to inclusions of protein aggregates in FTLD-tau cases, TDP-43, or Lewy bodies. Curcumin isoforms, conjugates and bio-available forms show affinity for the same Aβ structures. Curcumin staining overlaps with immunohistochemical detection of Aβ in fibrillar plaques and CAA, and to a lesser extent cored plaques. A weak staining of neurofibrillary tangles was observed, while other structures immunopositive for phosphorylated tau remained negative. In conclusion, curcumin, its isoforms, conjugates and bio-available forms selectively bind fibrillar Aβ in plaques and CAA in post mortem AD brain tissue. Curcumin, being a food additive with fluorescent properties, is therefore an interesting candidate for in-vivo diagnostics in AD, for example in retinal fluorescent imaging.http://link.springer.com/article/10.1186/s40478-018-0577-2CurcuminAmyloid-betaAlzheimer’s diseaseCerebral amyloid angiopathy (CAA)NeurodegenerationBiomarker
spellingShingle Jurre den Haan
Tjado H. J. Morrema
Annemieke J. Rozemuller
Femke H. Bouwman
Jeroen J. M. Hoozemans
Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer’s disease brains: Implications for in-vivo diagnostics
Acta Neuropathologica Communications
Curcumin
Amyloid-beta
Alzheimer’s disease
Cerebral amyloid angiopathy (CAA)
Neurodegeneration
Biomarker
title Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer’s disease brains: Implications for in-vivo diagnostics
title_full Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer’s disease brains: Implications for in-vivo diagnostics
title_fullStr Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer’s disease brains: Implications for in-vivo diagnostics
title_full_unstemmed Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer’s disease brains: Implications for in-vivo diagnostics
title_short Different curcumin forms selectively bind fibrillar amyloid beta in post mortem Alzheimer’s disease brains: Implications for in-vivo diagnostics
title_sort different curcumin forms selectively bind fibrillar amyloid beta in post mortem alzheimer s disease brains implications for in vivo diagnostics
topic Curcumin
Amyloid-beta
Alzheimer’s disease
Cerebral amyloid angiopathy (CAA)
Neurodegeneration
Biomarker
url http://link.springer.com/article/10.1186/s40478-018-0577-2
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