scholarly journals The Inflammasome Adaptor Protein ASC in Mild Cognitive Impairment and Alzheimer’s Disease

2020 ◽  
Vol 21 (13) ◽  
pp. 4674 ◽  
Author(s):  
Xavier O. Scott ◽  
Marisa E. Stephens ◽  
Marie C. Desir ◽  
W. Dalton Dietrich ◽  
Robert W. Keane ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Memory Loss ◽  
Adaptor Protein ◽  
Therapeutic Window ◽  
Likelihood Ratios ◽  
Predictive Values ◽  
Protein Levels

Mild cognitive impairment (MCI) is characterized by memory loss in the absence of dementia and is considered the translational stage between normal aging and early Alzheimer’s disease (AD). Patients with MCI have a greater risk of advancing to AD. Thus, identifying early markers of MCI has the potential to increase the therapeutic window to treat and manage the disease. Protein levels of the inflammasome signaling proteins apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and interleukin (IL)-18 were analyzed in the serum of patients with MCI, AD and healthy age-matched donors as possible biomarkers, as well as levels of soluble amyloid precursor proteins α/β (sAPP α/β) and neurofilament light (NfL). Cut-off points and positive and negative predictive values, as well as receiver operator characteristic (ROC) curves, likelihood ratios and accuracy were determined for these proteins. Although the levels of ASC were higher in MCI and AD than in age-matched controls, protein levels of ASC were higher in MCI than in AD cases. For control vs. MCI, the area under the curve (AUC) for ASC was 0.974, with a cut-off point of 264.9 pg/mL. These data were comparable to the AUC for sAPP α and β of 0.9687 and 0.9068, respectively, as well as 0.7734 for NfL. Moreover, similar results were obtained for control vs. AD and MCI vs. AD. These results indicate that ASC is a promising biomarker of MCI and AD.

DEF8 and Autophagy-Associated Genes are Altered in Mild Cognitive Impairment, Probable Alzheimer’s Disease Patients and a Transgenic Model of the Disease

2021 ◽  
pp. 1-16
Author(s):  
Esteban Leyton ◽  
Diego Matus ◽  
Sandra Espinoza ◽  
José Matías Benitez ◽  
Bastián I. Cortes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Real Time ◽  
Real Time Pcr ◽  
Mononuclear Cells ◽  
Differentially Expressed ◽  
Protein Levels ◽  
5Xfad Mice

Background: Disturbances in the autophagy/endolysosomal systems are proposed as early signatures of Alzheimer’s disease (AD). However, few studies are available concerning autophagy gene expression in AD patients. Objective: To explore the differential expression of classical genes involved in the autophagy pathway, among them a less characterized one, DEF8 (Differentially expressed in FDCP 8), initially considered a Rubicon family member, in peripheral blood mononuclear cells (PBMCs) from individuals with mild cognitive impairment (MCI) and probable AD (pAD) and correlate the results with the expression of DEF8 in the brain of 5xFAD mice. Method: By real-time PCR and flow cytometry, we evaluated autophagy genes levels in PBMCs from MCI and pAD patients. We evaluated DEF8 levels and its localization in brain samples of the 5xFAD mice by real-time PCR, western blot, and immunofluorescence. Results: Transcriptional levels of DEF8 were significantly reduced in PBMCs of MCI and pAD patients compared with healthy donors, correlating with the MoCA and MoCA-MIS cognitive tests scores. DEF8 protein levels were increased in lymphocytes from MCI but not pAD, compared to controls. In the case of brain samples from 5xFAD mice, we observed a reduced mRNA expression and augmented protein levels in 5xFAD compared to age-matched wild-type mice. DEF8 presented a neuronal localization. Conclusion: DEF8, a protein proposed to act at the final step of the autophagy/endolysosomal pathway, is differentially expressed in PBMCs of MCI and pAD and neurons of 5xFAD mice. These results suggest a potential role for DEF8 in the pathophysiology of AD.

scholarly journals Autophagy and mitophagy biomarkers are reduced in sera of patients with Alzheimer’s disease and mild cognitive impairment

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Massimiliano Castellazzi ◽  
Simone Patergnani ◽  
Mariapina Donadio ◽  
Carlotta Giorgi ◽  
Massimo Bonora ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Late Onset ◽  
Memory Loss ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Cellular Processes

AbstractDementia is a neurocognitive disorder characterized by a progressive memory loss and impairment in cognitive and functional abilities. Autophagy and mitophagy are two important cellular processes by which the damaged intracellular components are degraded by lysosomes. To investigate the contribution of autophagy and mitophagy in degenerative diseases, we investigated the serum levels of specific autophagic markers (ATG5 protein) and mitophagic markers (Parkin protein) in a population of older patients by enzyme-linked immunosorbent assay. Two hundred elderly (≥65 years) outpatients were included in the study: 40 (20 F and 20 M) with mild-moderate late onset Alzheimer’s disease (AD); 40 (20 F and 20 M) affected by vascular dementia (VAD); 40 with mild cognitive impairment (MCI); 40 (20 F and 20 M) with “mixed” dementia (MD); 40 subjects without signs of cognitive impairment were included as sex-matched controls. Our data indicated that, in serum samples, ATG5 and Parkin were both elevated in controls, and that VAD compared with AD, MCI and MD (all p < 0.01). Patients affected by AD, MD, and MCI showed significantly reduced circulating levels of both ATG5 and Parkin compared to healthy controls and VAD individuals, reflecting a significant down-regulation of autophagy and mitophagy pathways in these groups of patients. The measurement of serum levels of ATG5 and Parkin may represent an easily accessible diagnostic tool for the early monitoring of patients with cognitive decline.

scholarly journals Diagnosis of Alzheimer’s Disease with Ensemble Learning Classifier and 3D Convolutional Neural Network

Sensors ◽  
2021 ◽  
Vol 21 (22) ◽  
pp. 7634
Author(s):  
Peng Zhang ◽  
Shukuan Lin ◽  
Jianzhong Qiao ◽  
Yue Tu
Keyword(s):  
Neural Network ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Convolutional Neural Network ◽  
Ensemble Learning ◽  
Memory Loss ◽  
Main Tool ◽  
Disease Diagnosis

Alzheimer’s disease (AD), the most common type of dementia, is a progressive disease beginning with mild memory loss, possibly leading to loss of the ability to carry on a conversation and respond to environments. It can seriously affect a person’s ability to carry out daily activities. Therefore, early diagnosis of AD is conducive to better treatment and avoiding further deterioration of the disease. Magnetic resonance imaging (MRI) has become the main tool for humans to study brain tissues. It can clearly reflect the internal structure of a brain and plays an important role in the diagnosis of Alzheimer’s disease. MRI data is widely used for disease diagnosis. In this paper, based on MRI data, a method combining a 3D convolutional neural network and ensemble learning is proposed to improve the diagnosis accuracy. Then, a data denoising module is proposed to reduce boundary noise. The experimental results on ADNI dataset demonstrate that the model proposed in this paper improves the training speed of the neural network and achieves 95.2% accuracy in AD vs. NC (normal control) task and 77.8% accuracy in sMCI (stable mild cognitive impairment) vs. pMCI (progressive mild cognitive impairment) task in the diagnosis of Alzheimer’s disease.

scholarly journals An evaluation on changes in Hippocampus size for Cognitively Normal (CN), Mild Cognitive Impairment (MCI), and Alzheimer’s disease (AD) patients using Fuzzy Membership Function

2021 ◽  
Author(s):  
Ruhul Amin Hazarika ◽  
Arnab Kumar Maji ◽  
Debdatta Kandar ◽  
Prasun Chakrabarti ◽  
Tulika Chakrabarti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Memory Loss ◽  
Fuzzy Membership Function ◽  
Average Difference ◽  
Mr Images ◽  
Cognitively Normal ◽  
The Brain

Background: Alzheimer’s disease (AD) is a neurological disorder where the hippocampus in the brain gets affected severely. Hippocampus is a part of the limbic system, which is mainly responsible for forming memories. The transition from Cognitively Normal (CN) to AD is having one intermittent stage, popularly known as Mild Cognitive Impairment (MCI). In this study, segmentation operation has been performed first to separate the hippocampus, and then an analysis has been made on the basis of changes in area and atrophy in the hippocampus. A total of “2008” numbers of MR images have been analyzed for three different subject groups consist of “210” different subjects (Male:105, Female: 105) namely, CN, MCI, and AD.Objective: The objective of this study is to analyze the size and atrophy of the hippocampus due to AD and MCI in comparison with CN patients.Material and Methods: All the experiments have done using MATLAB tools. All the data used is acquired from the online dataset “Alzheimer’s Disease Neuroimaging Initiative (ADNI)”.Results: From the study, it is found that the average difference in the size of the hippocampus between CN and MCI is 17.05%, between CN and AD is 31.90%, and between MCI and AD is 18.24%. The average atrophy per year in the hippocampus is found to be as 4.62% for AD, 2.33% for MCI, and 1.10% for CN subjects.Conclusions: From the study, it is observed that, for AD patients, hippocampus atrophy is highest, and hence they experience the highest memory loss followed by the MCI and CN patients.

scholarly journals Herpesvirus infections and immunological disturbances in patients with different stages of Alzheimer’s disease

2021 ◽  
Vol 66 (2) ◽  
pp. 129-139
Author(s):  
S. A. Krynskiy ◽  
I. K. Malashenkova ◽  
D. P. Ogurtsov ◽  
N. A. Khailov ◽  
E. I. Chekulaeva ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Clinical Stage ◽  
Memory Loss ◽  
Control Group ◽  
Immunological Parameters ◽  
Humoral And Cellular Immunity

Introduction. Alzheimer’s disease (AD) is a multifactorial disease that leads to a progressive memory loss, visualspatial impairments, emotional and personality changes. As its earliest pre-dementia clinical stage, amnestic mild cognitive impairment syndrome (aMCI) is currently considered. Neuroinflammation plays a role in the development and progression of aMCI and the initial stage of AD, which can be supported by immunological disorders of a systemic character. Study of factors, including infections, influencing immune disorders and systemic inflammatory response in patients with aMCI, is of great importance.The aim of this study was to obtain new data on the possible role of herpesvirus infections in the development and progression of aMCI.Material and methods. 100 patients with aMCI diagnosis, 45 patients with AD, 40 people from the control group were enrolled into the study. The frequency of DNA detection of herpesviruses (Epstein–Barr virus (EBV), human herpesviruses (HHV) type 6 and 7, cytomegalovirus (CMV)), the levels of viral load and the serological markers of herpesvirus infections (IgG to HHV-1, IgG to CMV) were determined. Immunological studies included an assessment of the level of the main pro-inflammatory and anti-inflammatory cytokines, and indicators of humoral and cellular immunity.Results. The study found an increased detection rate of EBV in saliva and a higher level of EBV DNA in saliva in aMCI and AD than in the control group. A relationship between the presence of active EBV infection and changes in immunological parameters in patients with aMCI were found. It was also discovered that the level of IgG antibodies to CMV is associated with the stage of AD.Discussion. The results indicate a possible role of EBV- and CMV-induced infections in the development of immunological changes which are typical for mild cognitive impairment and in the progression of AD. Conclusion. The obtained data can be important for prognostic methods addressing AD development, including its pre-dementia stage, and for new approaches to individualized treatment and prevention.

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