Lipopolysaccharide, Identified Using an Antibody and by PAS Staining, Is Associated With Corpora amylacea and White Matter Injury in Alzheimer's Disease and Aging Brain

Corpora amylacea (CA) increase in number and size with aging. Their origins and functions remain unknown. Previously, we found that Alzheimer's disease (AD) brains have more CA in the periventricular white matter (PVWM) compared to aging controls. In addition, CA is associated with neurodegener...

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Autores principales:	Xinhua Zhan, Marisa Hakoupian, Lee-Way Jin, Frank R. Sharp
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	lipopolysaccharide vesicles Corpora amylacea white matter injury Alzheimer's disease neuroinflammation innate immune response Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/6c46251185e24a688e42f422d0fc1a49
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spelling	oai:doaj.org-article:6c46251185e24a688e42f422d0fc1a492021-11-30T19:21:20ZLipopolysaccharide, Identified Using an Antibody and by PAS Staining, Is Associated With Corpora amylacea and White Matter Injury in Alzheimer's Disease and Aging Brain1663-436510.3389/fnagi.2021.705594https://doaj.org/article/6c46251185e24a688e42f422d0fc1a492021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.705594/fullhttps://doaj.org/toc/1663-4365Corpora amylacea (CA) increase in number and size with aging. Their origins and functions remain unknown. Previously, we found that Alzheimer's disease (AD) brains have more CA in the periventricular white matter (PVWM) compared to aging controls. In addition, CA is associated with neurodegeneration as indicated by colocalization of degraded myelin basic protein (dMBP) with periodic acid-Schiff (PAS), a CA marker. We also found that bacterial lipopolysaccharide is present in aging brains, with more LPS in AD compared with controls. Periodic acid-Schiff staining is used to identify CA by virtue of their high polysaccharide content. Despite the growing knowledge of CA as a contributor to AD pathology, the molecules that contribute to the polysaccharides in CA are not known. Notably, lipopolysaccharides (LPS) are important cell-surface polysaccharides found in all Gram-negative bacteria. However, it is unknown whether PAS could detect LPS, whether the LPS found in aging brains contribute to the polysaccharide found in CA, and whether LPS associate with myelin injury. In this study, we found that aging brains had a myelin deficit zone (MDZ) adjacent to the ventricles in PVWM. The MDZ contained vesicles, most of which were CA. LPS and dMBP levels were higher in AD than in control brains. LPS was colocalized with dMBP in the vesicles/CA, linking white matter injury with a bacterial pro-inflammatory molecule. The vesicles also contained oxidized fibers, C-reactive protein, NG2, and GALC, markers of oligodendrocyte precursor cells (OPCs) and oligodendrocyte cells (OLs), respectively. The vesicles/CA were surrounded by dense astrocyte processes in control and AD brains. LPS was co-localized with CA by double staining of PAS with LPS in aging brains. The relationship of LPS with PAS staining was confirmed by PAS staining of purified LPS on nitrocellulose membranes. These findings reveal that LPS is one of the polysaccharides found in CA which can be stained with PAS. In addition, vesicles/CA are associated with oxidized and damaged myelin. The LPS in these vesicles/CA may have contributed to this oxidative myelin damage and may have contributed to oxidative stress to OPCs and OLs which could impair the ability to repair damaged myelin in AD and control brains.Xinhua ZhanMarisa HakoupianLee-Way JinFrank R. SharpFrontiers Media S.A.articlelipopolysaccharide vesiclesCorpora amylaceawhite matter injuryAlzheimer's diseaseneuroinflammationinnate immune responseNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lipopolysaccharide vesicles Corpora amylacea white matter injury Alzheimer's disease neuroinflammation innate immune response Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	lipopolysaccharide vesicles Corpora amylacea white matter injury Alzheimer's disease neuroinflammation innate immune response Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Xinhua Zhan Marisa Hakoupian Lee-Way Jin Frank R. Sharp Lipopolysaccharide, Identified Using an Antibody and by PAS Staining, Is Associated With Corpora amylacea and White Matter Injury in Alzheimer's Disease and Aging Brain
description	Corpora amylacea (CA) increase in number and size with aging. Their origins and functions remain unknown. Previously, we found that Alzheimer's disease (AD) brains have more CA in the periventricular white matter (PVWM) compared to aging controls. In addition, CA is associated with neurodegeneration as indicated by colocalization of degraded myelin basic protein (dMBP) with periodic acid-Schiff (PAS), a CA marker. We also found that bacterial lipopolysaccharide is present in aging brains, with more LPS in AD compared with controls. Periodic acid-Schiff staining is used to identify CA by virtue of their high polysaccharide content. Despite the growing knowledge of CA as a contributor to AD pathology, the molecules that contribute to the polysaccharides in CA are not known. Notably, lipopolysaccharides (LPS) are important cell-surface polysaccharides found in all Gram-negative bacteria. However, it is unknown whether PAS could detect LPS, whether the LPS found in aging brains contribute to the polysaccharide found in CA, and whether LPS associate with myelin injury. In this study, we found that aging brains had a myelin deficit zone (MDZ) adjacent to the ventricles in PVWM. The MDZ contained vesicles, most of which were CA. LPS and dMBP levels were higher in AD than in control brains. LPS was colocalized with dMBP in the vesicles/CA, linking white matter injury with a bacterial pro-inflammatory molecule. The vesicles also contained oxidized fibers, C-reactive protein, NG2, and GALC, markers of oligodendrocyte precursor cells (OPCs) and oligodendrocyte cells (OLs), respectively. The vesicles/CA were surrounded by dense astrocyte processes in control and AD brains. LPS was co-localized with CA by double staining of PAS with LPS in aging brains. The relationship of LPS with PAS staining was confirmed by PAS staining of purified LPS on nitrocellulose membranes. These findings reveal that LPS is one of the polysaccharides found in CA which can be stained with PAS. In addition, vesicles/CA are associated with oxidized and damaged myelin. The LPS in these vesicles/CA may have contributed to this oxidative myelin damage and may have contributed to oxidative stress to OPCs and OLs which could impair the ability to repair damaged myelin in AD and control brains.
format	article
author	Xinhua Zhan Marisa Hakoupian Lee-Way Jin Frank R. Sharp
author_facet	Xinhua Zhan Marisa Hakoupian Lee-Way Jin Frank R. Sharp
author_sort	Xinhua Zhan
title	Lipopolysaccharide, Identified Using an Antibody and by PAS Staining, Is Associated With Corpora amylacea and White Matter Injury in Alzheimer's Disease and Aging Brain
title_short	Lipopolysaccharide, Identified Using an Antibody and by PAS Staining, Is Associated With Corpora amylacea and White Matter Injury in Alzheimer's Disease and Aging Brain
title_full	Lipopolysaccharide, Identified Using an Antibody and by PAS Staining, Is Associated With Corpora amylacea and White Matter Injury in Alzheimer's Disease and Aging Brain
title_fullStr	Lipopolysaccharide, Identified Using an Antibody and by PAS Staining, Is Associated With Corpora amylacea and White Matter Injury in Alzheimer's Disease and Aging Brain
title_full_unstemmed	Lipopolysaccharide, Identified Using an Antibody and by PAS Staining, Is Associated With Corpora amylacea and White Matter Injury in Alzheimer's Disease and Aging Brain
title_sort	lipopolysaccharide, identified using an antibody and by pas staining, is associated with corpora amylacea and white matter injury in alzheimer's disease and aging brain
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6c46251185e24a688e42f422d0fc1a49
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Lipopolysaccharide, Identified Using an Antibody and by PAS Staining, Is Associated With Corpora amylacea and White Matter Injury in Alzheimer's Disease and Aging Brain

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