scholarly journals Immunohistochemical Analysis of Activin Receptor-Like Kinase 1 (ACVRL1/ALK1) Expression in the Rat and Human Hippocampus: Decline in CA3 During Progression of Alzheimer’s Disease

2018 ◽  
Vol 63 (4) ◽  
pp. 1433-1443 ◽  
Author(s):  
Stephanie L. Adams ◽  
Laurent Benayoun ◽  
Kathy Tilton ◽  
Tiffany J. Mellott ◽  
Sudha Seshadri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immunohistochemical Analysis ◽  
Activin Receptor ◽  
Human Hippocampus ◽  
Receptor Like Kinase

scholarly journals The Expression of Activin Receptor-Like Kinase 1 (ACVRL1/ALK1) in Hippocampal Arterioles Declines During Progression of Alzheimer’s Disease

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Kelley E Anderson ◽  
Thomas A Bellio ◽  
Emily Aniskovich ◽  
Stephanie L Adams ◽  
Jan Krzysztof Blusztajn ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Vessels ◽  
Pyramidal Neurons ◽  
Brain Parenchyma ◽  
Amyloid Angiopathy ◽  
Type I ◽  
Clinical Dementia Rating ◽  
Activin Receptor ◽  
Receptor Like Kinase

Abstract Cerebral amyloid angiopathy (CAA) in Alzheimer’s disease (AD)—deposition of beta amyloid (Aβ) within the walls of cerebral blood vessels—typically accompanies Aβ buildup in brain parenchyma and causes abnormalities in vessel structure and function. We recently demonstrated that the immunoreactivity of activin receptor-like kinase 1 (ALK1), the type I receptor for circulating BMP9/BMP10 (bone morphogenetic protein) signaling proteins, is reduced in advanced, but not early stages of AD in CA3 pyramidal neurons. Here we characterize vascular expression of ALK1 in the context of progressive AD pathology accompanied by amyloid angiopathy in postmortem hippocampi using immunohistochemical methods. Hippocampal arteriolar wall ALK1 signal intensity was 35% lower in AD patients (Braak and Braak Stages IV and V [BBIV-V]; clinical dementia rating [CDR1-2]) as compared with subjects with early AD pathologic changes but either cognitively intact or with minimal cognitive impairment (BBIII; CDR0-0.5). The intensity of Aβ signal in arteriolar walls was similar in all analyzed cases. These data suggest that, as demonstrated previously for specific neuronal populations, ALK1 expression in blood vessels is also vulnerable to the AD pathophysiologic process, perhaps related to CAA. However, cortical arterioles may remain responsive to the ALK1 ligands, such as BMP9 and BMP10 in early and moderate AD.

scholarly journals DNA methylation signature of human hippocampus in Alzheimer’s disease is linked to neurogenesis

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Miren Altuna ◽  
Amaya Urdánoz-Casado ◽  
Javier Sánchez-Ruiz de Gordoa ◽  
María V. Zelaya ◽  
Alberto Labarga ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Human Hippocampus

scholarly journals Metabolic Profiling of Suprachiasmatic Nucleus Reveals Multifaceted Effects in an Alzheimer’s Disease Mouse Model

2021 ◽  
pp. 1-12
Author(s):  
Muhamed N.H. Eeza ◽  
Rico Singer ◽  
Corinna Höfling ◽  
Jörg Matysik ◽  
Huub J.M. de Groot ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Metabolic Profiling ◽  
Inflammatory Responses ◽  
Immunohistochemical Analysis ◽  
Magic Angle Spinning ◽  
Tg2576 Mouse ◽  
Magic Angle ◽  
Gaba Production

Background: Circadian rhythm disturbance is commonly observed in Alzheimer’s disease (AD). In mammals, these rhythms are orchestrated by the superchiasmatic nucleus (SCN). Our previous study in the Tg2576 AD mouse model suggests that inflammatory responses, most likely manifested by low GABA production, may be one of the underlying perpetrators for the changes in circadian rhythmicity and sleep disturbance in AD. However, the mechanistic connections between SCN dysfunction, GABA modulation, and inflammation in AD is not fully understood. Objective: To reveal influences of amyloid pathology in Tg2576 mouse brain on metabolism in SCN and to identify key metabolic sensors that couple SCN dysfunction with GABA modulation and inflammation. Methods: High resolution magic angle spinning (HR-MAS) NMR in conjunction with multivariate analysis was applied for metabolic profiling in SCN of control and Tg2576 female mice. Immunohistochemical analysis was used to detect neurons, astrocytes, expression of GABA transporter 1 (GAT1) and Bmal1. Results: Metabolic profiling revealed significant metabolic deficits in SCN of Tg2576 mice. Reductions in glucose, glutamate, GABA, and glutamine provide hints toward an impaired GABAergic glucose oxidation and neurotransmitter cycling in SCN of AD mice. In addition, decreased redox co-factor NADPH and glutathione support a redox disbalance. Immunohistochemical examinations showed low expression of the core clock gene, Bmal1, especially in activated astrocytes. Moreover, decreased expression of GAT1 in astrocytes indicates low GABA recycling in this cell type. Conclusion: Our results suggest that redox disbalance and compromised GABA signaling are important denominators and connectors between neuroinflammation and clock dysfunction in AD.

scholarly journals High field magnetic resonance microscopy of the human hippocampus in Alzheimer's disease: Quantitative imaging and correlation with iron

NeuroImage ◽  
2012 ◽  
Vol 59 (2) ◽  
pp. 1249-1260 ◽  
Author(s):  
Vijay Antharam ◽  
Joanna F. Collingwood ◽  
John-Paul Bullivant ◽  
Mark R. Davidson ◽  
Saurav Chandra ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Magnetic Resonance ◽  
High Field ◽  
Quantitative Imaging ◽  
Magnetic Resonance Microscopy ◽  
Human Hippocampus

scholarly journals Collusion of α-Synuclein and Aβ aggravating co-morbidities in a novel prion-type mouse model

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Grace M. Lloyd ◽  
Jess-Karan S. Dhillon ◽  
Kimberly-Marie M. Gorion ◽  
Cara Riffe ◽  
Susan E. Fromholt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lewy Body ◽  
Amyloid Β ◽  
Lewy Body Dementia ◽  
Immunohistochemical Analysis ◽  
Aggregation Kinetics ◽  
Current Area ◽  
Old Mice ◽  
A Current

Abstract Background The misfolding of host-encoded proteins into pathological prion conformations is a defining characteristic of many neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and Lewy body dementia. A current area of intense study is the way in which the pathological deposition of these proteins might influence each other, as various combinations of co-pathology between prion-capable proteins are associated with exacerbation of disease. A spectrum of pathological, genetic and biochemical evidence provides credence to the notion that amyloid β (Aβ) accumulation can induce and promote α-synuclein pathology, driving neurodegeneration. Methods To assess the interplay between α-synuclein and Aβ on protein aggregation kinetics, we crossed mice expressing human α-synuclein (M20) with APPswe/PS1dE9 transgenic mice (L85) to generate M20/L85 mice. We then injected α-synuclein preformed fibrils (PFFs) unilaterally into the hippocampus of 6-month-old mice, harvesting 2 or 4 months later. Results Immunohistochemical analysis of M20/L85 mice revealed that pre-existing Aβ plaques exacerbate the spread and deposition of induced α-synuclein pathology. This process was associated with increased neuroinflammation. Unexpectedly, the injection of α-synuclein PFFs in L85 mice enhanced the deposition of Aβ; whereas the level of Aβ deposition in M20/L85 bigenic mice, injected with α-synuclein PFFs, did not differ from that of mice injected with PBS. Conclusions These studies reveal novel and unexpected interplays between α-synuclein pathology, Aβ and neuroinflammation in mice that recapitulate the pathology of Alzheimer’s disease and Lewy body dementia.

Cerebral Ischemia and Alzheimer's Disease: The Expression of Amyloid-β and Apolipoprotein E in Human Hippocampus

2007 ◽  
Vol 12 (4) ◽  
pp. 335-341 ◽  
Author(s):  
Ji-ping Qi ◽  
He Wu ◽  
Yi Yang ◽  
Dan-dan Wang ◽  
Yan-xi Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Ischemia ◽  
Apolipoprotein E ◽  
Amyloid Β ◽  
Human Hippocampus

scholarly journals Protein Expression of Alzheimer's disease‐ and Reduced Hippocampal Volume‐ Risk Loci in Human Hippocampus

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Stephanie Adams ◽  
Tim Norman ◽  
Kathy Tilton ◽  
Sudha Seshadri ◽  
Ivana Delalle
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Expression ◽  
Hippocampal Volume ◽  
Human Hippocampus

Transcriptome-To-Metabolome™ Biosimulation Reveals Human Hippocampal Hypometabolism with Age and Alzheimer’s Disease

2011 ◽  
Vol 2 (2) ◽  
pp. 1-18
Author(s):  
Clyde F. Phelix ◽  
Richard G. LeBaron ◽  
Dawnlee J. Roberson ◽  
Rosa E. Villanueva ◽  
Greg Villareal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Metabolism ◽  
Metabolic Pathways ◽  
Cholesterol Metabolism ◽  
Aging Male ◽  
Glucose And Lipid Metabolism ◽  
Human Hippocampus ◽  
Molecular Studies

The authors had validated a proprietary method, Transcriptome-To-Metabolome™ (TTM™) Biosimulation, for using the transcriptome to determine parameters for kinetic biosimulation of 16 core metabolic pathways. In vivo and in silico evidence confirmed that hippocampal cholesterol metabolism decreases with aging and increases with Alzheimer’s disease (AD). The molecular studies on aging primate and human hippocampus, including AD samples, provided internal validations on the biosimulations, while evidence from the literature, bibliome, provided external validations. This study extends the investigations with the TTM™ Biosimulations into the changes in these 16 metabolic pathways in aging male human hippocampus and for stages of AD. The authors report robust hippocampal hypometabolism in the fifth to tenth decade of life involving glucose and lipid metabolism in male humans. These findings are validated externally from the bibliome. Several changes in AD are demonstrated to be exaggerations or deviations of very late stage changes of normal aging among these pathways.

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