scholarly journals Overexpression of HIF-2α in Alzheimer's disease Resilient Patients

2020 ◽  
Author(s):  
Vivianne Mitri
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dentate Gyrus ◽  
Pyramidal Neurons ◽  
Amyloid Plaques ◽  
Stratum Radiatum ◽  
Alzheimers Disease ◽  
Cytoplasmic Staining ◽  
Neuronal Nuclei ◽  
Hypoxic Conditions

Alzheimers disease (AD) Resilient individuals are characterized by having a degree of amyloid plaques at level with that of demented individuals, but a reduced amount of abnormal neurofibrillary protein tangles (NFTs). NFTs, also known to be upregulated under hypoxic conditions, become clinically relevant when involved in the stratum radiatum. In this paper, we show this region and more to have significant increases of hypoxic adaptive protein, HIF-2α, within AD resilient cases. Pericyte staining was present in the stratum lacunosum and radiatum of all cases affected by AD pathology (n = 4) but in AD resilient cases were increased by 12-fold (n=3) p<.0001. No staining was detected in normal cases (n=2). HIF-2α was also only present in hippocampal neuronal nuclei of AD resilient cases, including the dentate gyrus and CA1. Cytoplasmic staining of pyramidal neurons within the subiculum was seen in all cases affected by AD pathology. The intensity of HIF-2α appears to be specific to known regions of protection in AD resilience and to increase on a gradient that corresponds to protection against dementia. These results also highlight the stratum lacunosum and radiatum as regions critically impacted by hypoxic insult among AD cases.

scholarly journals Effects of Inducing Gamma Oscillations in Hippocampal Subregions DG, CA3, and CA1 on the Potential Alleviation of Alzheimer’s Disease-Related Pathology: Computer Modeling and Simulations

Entropy ◽  
2019 ◽  
Vol 21 (6) ◽  
pp. 587
Author(s):  
Dariusz Świetlik ◽  
Jacek Białowąs ◽  
Janusz Moryś ◽  
Ilona Klejbor ◽  
Aida Kusiak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dentate Gyrus ◽  
Pyramidal Neurons ◽  
Gamma Oscillations ◽  
Control Model ◽  
Transfer Entropy ◽  
Ca1 Region ◽  
Pathological Model ◽  
The One

The aim of this study was to evaluate the possibility of the gamma oscillation function (40–130 Hz) to reduce Alzheimer’s disease related pathology in a computer model of the hippocampal network dentate gyrus, CA3, and CA1 (DG-CA3-CA1) regions. Methods: Computer simulations were made for a pathological model in which Alzheimer’s disease was simulated by synaptic degradation in the hippocampus. Pathology modeling was based on sequentially turning off the connections with entorhinal cortex layer 2 (EC2) and the dentate gyrus on CA3 pyramidal neurons. Gamma induction modeling consisted of simulating the oscillation provided by the septo-hippocampal pathway with band frequencies from 40–130 Hz. Pathological models with and without gamma induction were compared with a control. Results: In the hippocampal regions of DG, CA3, and CA1, and jointly DG-CA3-CA1 and CA3-CA1, gamma induction resulted in a statistically significant improvement in terms of increased numbers of spikes, spikes per burst, and burst duration as compared with the model simulating Alzheimer’s disease (AD). The positive maximal Lyapunov exponent was negative in both the control model and the one with gamma induction as opposed to the pathological model where it was positive within the DG-CA3-CA1 region. Gamma induction resulted in decreased transfer entropy in accordance with the information flow in DG → CA3 and CA3 → CA1. Conclusions: The results of simulation studies show that inducing gamma oscillations in the hippocampus may reduce Alzheimer’s disease related pathology. Pathologically higher transfer entropy values after gamma induction returned to values comparable to the control model.

Aβ42-positive non-pyramidal neurons around amyloid plaques in Alzheimer's disease

The Lancet ◽  
2000 ◽  
Vol 355 (9197) ◽  
pp. 42-43 ◽  
Author(s):  
Akihide Mochizuki ◽  
Akira Tamaoka ◽  
Atsushi Shimohata ◽  
Yasuko Komatsuzaki ◽  
Shin'ichi Shoji
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pyramidal Neurons ◽  
Amyloid Plaques

scholarly journals Characterizing the human hippocampus in aging and Alzheimer’s disease using a computational atlas derived from ex vivo MRI and histology

2018 ◽  
Vol 115 (16) ◽  
pp. 4252-4257 ◽  
Author(s):  
Daniel H. Adler ◽  
Laura E. M. Wisse ◽  
Ranjit Ittyerah ◽  
John B. Pluta ◽  
Song-Lin Ding ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dentate Gyrus ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Stratum Radiatum ◽  
Aging Effects ◽  
Hippocampal Subfields ◽  
Mri Scans

Although the hippocampus is one of the most studied structures in the human brain, limited quantitative data exist on its 3D organization, anatomical variability, and effects of disease on its subregions. Histological studies provide restricted reference information due to their 2D nature. In this paper, high-resolution (∼200 × 200 × 200 μm3) ex vivo MRI scans of 31 human hippocampal specimens are combined using a groupwise diffeomorphic registration approach into a 3D probabilistic atlas that captures average anatomy and anatomic variability of hippocampal subfields. Serial histological imaging in 9 of the 31 specimens was used to label hippocampal subfields in the atlas based on cytoarchitecture. Specimens were obtained from autopsies in patients with a clinical diagnosis of Alzheimer's disease (AD; 9 subjects, 13 hemispheres), of other dementia (nine subjects, nine hemispheres), and in subjects without dementia (seven subjects, nine hemispheres), and morphometric analysis was performed in atlas space to measure effects of age and AD on hippocampal subfields. Disproportional involvement of the cornu ammonis (CA) 1 subfield and stratum radiatum lacunosum moleculare was found in AD, with lesser involvement of the dentate gyrus and CA2/3 subfields. An association with age was found for the dentate gyrus and, to a lesser extent, for CA1. Three-dimensional patterns of variability and disease and aging effects discovered via the ex vivo hippocampus atlas provide information highly relevant to the active field of in vivo hippocampal subfield imaging.

scholarly journals Increased astrocyte representation in the hippocampus of 5xFAD mice

2021 ◽  
Vol 72 (2) ◽  
pp. 5-10
Author(s):  
Violeta Jovanović ◽  
Jelica Despotović ◽  
Mario Balo ◽  
Ivan Zaletel ◽  
Sanja Despotović ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dentate Gyrus ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Amyloid Plaques ◽  
Control Group ◽  
Significant Difference ◽  
5Xfad Mice ◽  
And Control

Introduction: Alzheimer's disease is the most common neurodegenerative disorder, characterized by the formation of amyloid plaques and the neurofibrillary tangles in the brain of an ill person, leading to neuronal damage and loss. Activation of astrocytes and astrogliosis occurs along with this process. Due to ethical limitations in working with human tissue, numerous transgenic animal models have been developed to study the pathogenesis of these processes. Early Ab deposition is observed in the cortex and the hippocampus. Aim: This study aimed to determine the difference in the presence of GFAP positive cells in the hippocampus between transgenic 5xFAD mice aged 36 weeks and their corresponding controls. Material and Methods: The 5xFAD mice model of Alzheimer's disease was used, characterized by early formation of amyloid plaques but without the presence of neurofibrillar tangles. Transgenic and control animals were sacrificed at 36 weeks of age. The visualization of GFAP-positive cells in the hippocampus of their brains was done by using immunohistochemistry and antibody for glial fibrillary acidic protein - GFAP, the major marker of astrocytes. Quantification of immuno-reactivity was done by using the Icy software system. Results: There was a statistically significant difference in the expression of GFAP in the dentate gyrus and the granular zone of the hippocampus between the transgenic and control group at 36 weeks of age, while the significant change in the CA1-3 regions was not observed between investigated groups. Conclusion: Obtained results confirm the involvement of astrogliosis in the pathophysiology of Alzheimer's disease and indicate an earlier occurrence of astrogliosis in the dentate gyrus and granular zone, in relation to other regions of the hippocampus, in the 36-week-old 5xFAD mice.

Synthesis of a Novel Curcumin Derivative as a Potential Imaging Probe in Alzheimer’s Disease Imaging

2019 ◽  
Vol 16 (8) ◽  
pp. 723-731 ◽  
Author(s):  
Alexander Sturzu ◽  
Sumbla Sheikh ◽  
Hubert Kalbacher ◽  
Thomas Nägele ◽  
Christopher Weidenmaier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Flow Cytometry ◽  
Transgenic Mice ◽  
Ex Vivo ◽  
Amyloid Plaques ◽  
Laser Scanning Microscopy ◽  
Β Amyloid ◽  
Curcumin Derivative

Background: Curcumin has been of interest in the field of Alzheimer’s disease. Early studies on transgenic mice showed promising results in the reduction of amyloid plaques.However, curcumin is very poorly soluble in aqueous solutions and not easily accessible to coupling as it contains only phenolic groups as potential coupling sites. For these reasons only few imaging studies using curcumin bound as an ester were performed and curcumin is mainly used as nutritional supplement. Methods: In the present study we produced an aminoethyl ether derivative of curcumin using a nucleophilic substitution reaction. This is a small modification and should not impact the properties of curcumin while introducing an easily accessible reactive amino group. This novel compound could be used to couple curcumin to other molecules using the standard methods of peptide synthesis. We studied the aminoethyl-curcumin compound and a tripeptide carrying this aminoethyl-curcumin and the fluorescent dye fluorescein (FITC-curcumin) in vitro on cell culture using confocal laser scanning microscopy and flow cytometry. Then these two substances were tested ex vivo on brain sections prepared from transgenic mice depicting Alzheimer-like β-amyloid plaques. Results: In the in vitro CLSM microscopy and flow cytometry experiments we found dot-like unspecific uptake and only slight cytotoxicity correlating with this uptake. As these measurements were optimized for the use of fluorescein as dye we found that the curcumin at 488nm fluorescence excitation was not strong enough to use it as a fluorescence marker in these applications. In the ex vivo sections CLSM experiments both the aminoethyl-curcumin and the FITC-curcumin peptide bound specifically to β- amyloid plaques. Conclusion: In conclusion we successfully produced a novel curcumin derivative which could easily be coupled to other imaging or therapeutic molecules as a sensor for amyloid plaques.

scholarly journals In vivo multi-parametric manganese-enhanced MRI for detecting amyloid plaques in rodent models of Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eugene Kim ◽  
Davide Di Censo ◽  
Mattia Baraldo ◽  
Camilla Simmons ◽  
Ilaria Rosa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Plaques ◽  
Transgenic Animals ◽  
Surrounding Tissue ◽  
Rodent Models ◽  
Enhanced Mri ◽  
5Xfad Mice ◽  
Manganese Enhanced Mri

AbstractAmyloid plaques are a hallmark of Alzheimer’s disease (AD) that develop in its earliest stages. Thus, non-invasive detection of these plaques would be invaluable for diagnosis and the development and monitoring of treatments, but this remains a challenge due to their small size. Here, we investigated the utility of manganese-enhanced MRI (MEMRI) for visualizing plaques in transgenic rodent models of AD across two species: 5xFAD mice and TgF344-AD rats. Animals were given subcutaneous injections of MnCl2 and imaged in vivo using a 9.4 T Bruker scanner. MnCl2 improved signal-to-noise ratio but was not necessary to detect plaques in high-resolution images. Plaques were visible in all transgenic animals and no wild-types, and quantitative susceptibility mapping showed that they were more paramagnetic than the surrounding tissue. This, combined with beta-amyloid and iron staining, indicate that plaque MR visibility in both animal models was driven by plaque size and iron load. Longitudinal relaxation rate mapping revealed increased manganese uptake in brain regions of high plaque burden in transgenic animals compared to their wild-type littermates. This was limited to the rhinencephalon in the TgF344-AD rats, while it was most significantly increased in the cortex of the 5xFAD mice. Alizarin Red staining suggests that manganese bound to plaques in 5xFAD mice but not in TgF344-AD rats. Multi-parametric MEMRI is a simple, viable method for detecting amyloid plaques in rodent models of AD. Manganese-induced signal enhancement can enable higher-resolution imaging, which is key to visualizing these small amyloid deposits. We also present the first in vivo evidence of manganese as a potential targeted contrast agent for imaging plaques in the 5xFAD model of AD.

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