scholarly journals 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

2021 ◽  
Vol 13 ◽  
Author(s):  
Xinhua Zhan ◽  
Marisa Hakoupian ◽  
Lee-Way Jin ◽  
Frank R. Sharp
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Periodic Acid ◽  
White Matter Injury ◽  
Aging Brain ◽  
Periventricular White Matter ◽  
Corpora Amylacea ◽  
Periodic Acid Schiff ◽  
Pas Staining

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.

P2-023: White matter injury and the orphan c2orf40 gene encoding Ecrg4 in Alzheimer's disease

2013 ◽  
Vol 9 ◽  
pp. P352-P353
Author(s):  
Sonia Podvin ◽  
Miles Miller ◽  
Ryan Rossi ◽  
Jasmine Chukwueke ◽  
Ji Sook Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
White Matter Injury ◽  
Gene Encoding

The Diagnostic Value of Multi Ultra High-b-value DWI for Alzheimer’s Disease

2021 ◽  
Author(s):  
Tianxiu Zheng ◽  
Qiuyan Chen ◽  
Yanhua Qiu ◽  
Deyong Zhang ◽  
Liwei Shi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
B Value ◽  
Diagnostic Value ◽  
White Matter Hyperintensity ◽  
Periventricular White Matter ◽  
High B Value ◽  
Left Hippocampus ◽  
Hippocampus Volume

Abstract To evaluate the diagnostic value of multi-ultra high b-value diffusion-weighted imaging (UHBV-DWI) in Alzheimer’s disease (AD), and to build a regression prediction modelfor AD.90 participants including 30 AD, 30 mild cognitive impairments (MCI) and 30 volunteers without neurological diseases were enrolled to perform with hippocampal volume, white matter hyperintensities volume (WMH volume), periventricular white matter hyperintensity (PVWMH) score, deep white matter hyperintensity (DWMH) score and UHBV-DWI.We found UHBV-DWI outperformed in the diagnosis of AD (AUC = 0.858), and multiple linear regression model: y = 0.515 + 0.018 *(WMH volume) + 0.221 *(ADCuh value)-0.359 *(left hippocampus volume) were established.So we came to a conclusion: UHBV-DWI is helpful for diagnosing AD, and the combination of WMH volume and left hippocampus volume has a better diagnostic performance.

Parahippocampal corpora amylacea and neuronal lipofuscin in human aging

Open Medicine ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. 749-761
Author(s):  
Mirjana Bakić ◽  
Ivan Jovanović ◽  
Slađana Ugrenović ◽  
Ljiljana Vasović ◽  
Miljan Krstić ◽  
...  
Keyword(s):  
Periodic Acid ◽  
Age Groups ◽  
Neuron Specific Enolase ◽  
Parahippocampal Gyrus ◽  
Aging Brain ◽  
Numerical Density ◽  
Corpora Amylacea ◽  
Periodic Acid Schiff ◽  
Morphometric Analyses ◽  
Altered Metabolism

AbstractThe aim of this research was to quantify the number of corpora amylacea and lipofuscin-bearing neurons in the parahippocampal region of the brain. Right parahippocampal gyrus specimens of 30 cadavers were used as material for histological and morphometric analyses. A combined Alcian Blue and Periodic Acid-Schiff technique was used for identification and quantification of corpora amylacea and lipofuscin-bearing neurons. Immunohistochemistry was performed using S100 polyclonal, neuron-specific enolase and glial fibrillary acidic protein monoclonal antibodies for differentiation of corpora amylacea and other spherical inclusions of the aging brain. Cluster analysis of obtained data showed the presence of three age groups (median age: I = 41.5, II = 68, III = 71.5). The second group was characterized by a significantly higher numerical density of subcortical corpora amylacea and number of lipofuscin-bearing neurons than other two groups. Values of the latter cited parameters in the third group were insignificantly higher than the first younger group. Linear regression showed that number of parahippocampal lipofuscin-bearing neurons significantly predicts numerical density of subcortical corpora amylacea. The above results suggest that more numerous parahippocampal region corpora amylacea and lipofuscin-bearing neurons in some older cases might represent signs of its’ neurons quantitatively-altered metabolism.

scholarly journals Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer’s disease-like pathology

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
David Baglietto-Vargas ◽  
Stefania Forner ◽  
Lena Cai ◽  
Alessandra C. Martini ◽  
Laura Trujillo-Estrada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Autosomal Dominant ◽  
Late Onset ◽  
Periodic Acid ◽  
Wild Type ◽  
Periodic Acid Schiff ◽  
Human Counterpart ◽  
Age Dependent

AbstractThe majority of Alzheimer’s disease (AD) cases are late-onset and occur sporadically, however most mouse models of the disease harbor pathogenic mutations, rendering them better representations of familial autosomal-dominant forms of the disease. Here, we generated knock-in mice that express wildtype human Aβ under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Aβ sequence to its wild-type human counterpart leads to age-dependent impairments in cognition and synaptic plasticity, brain volumetric changes, inflammatory alterations, the appearance of Periodic Acid-Schiff (PAS) granules and changes in gene expression. In addition, when exon 14 encoding the Aβ sequence was flanked by loxP sites we show that Cre-mediated excision of exon 14 ablates hAβ expression, rescues cognition and reduces the formation of PAS granules.

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