scholarly journals Multi-regional Neurodegeneration in Alzheimer’s disease: Meta-analysis and data integration of transcriptomics data

2018 ◽  
Author(s):  
Karbalaei Reza ◽  
Rezaei-Tavirani Mostafa ◽  
Torkzaban Bahareh ◽  
Azimzadeh Sadegh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metabolic Pathways ◽  
Analytical Study ◽  
Meta Analysis ◽  
Brain Regions ◽  
Regulatory Pathways ◽  
Transcriptomics Data ◽  
The Brain

AbstractAlzheimer’s disease (AD) is a complex neurodegenerative disease with various deleterious perturbations in regulatory pathways of various brain regions. Thus, it would be critical to understanding the role of different regions of the brain in initiation and progression of AD, However, owing to complex and multifactorial nature of this disease, the molecular mechanism of AD has yet to be fully elucidated. To confront with this challenge, we launched a meta-analytical study of current transcriptomics data in four different regions of the brain in AD (Entorhinal, Hippocampus, Temporal and Frontal) with systems analysis of identifying involved signaling and metabolic pathways. We found different regulatory patterns in Entorhinal and Hippocampus regions to be associated with progression of AD. We also identified shared versus unique biological pathways and critical proteins among different brain regions. ACACB, GAPDH, ACLY, and EGFR were the most important proteins in Entorhinal, Frontal, Hippocampus and Temporal regions, respectively. Moreover, eight proteins including CDK5, ATP5G1, DNM1, GNG3, AP2M1, ALDOA, GPI, and TPI1 were differentially expressed in all four brain regions, among which, CDK5 and ATP5G1 were enriched in KEGG Alzheimer’s disease pathway as well.

scholarly journals The role of metabolic syndrome in Alzheimer’s disease

2021 ◽  
Author(s):  
Gláucia Maria Senhorinha ◽  
Arlys Emanuel Mendes da Silva Santos ◽  
Douglas Daniel Dophine
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Metabolic Syndrome ◽  
Brain Regions ◽  
Alzheimer Dementia ◽  
The Metabolic Syndrome ◽  
The Brain

Background: Metabolic syndrome (MS) leads to the deposits formation of insoluble protein aggregates, neuroinflammation, oxidative stress, neuronal insulin resistance, progressive insulin resistance, desensitization and β-amyloid amyloidosis in the brain, besides direct ischemic effects which are closely associated with Alzheimer’s disease (AD).1 Objectives: The present study seeks to understand the role of the metabolic syndrome in the pathophysiology of Alzheimer’s disease and to describe preventive and therapeutic interventions. Methods: PUBMED and Web of Science were the databases used, the following descriptors were used to search the articles: “Alzheimer Disease” OR “Alzheimer Dementia” AND “Metabolic Syndrome”. Results: The studies in general have shown that MS is related to AD through brain insulin resistance, triggered by oxidative stress and neuroinflammation. It is related to the progressive atrophy of brain regions involved in the progression of AD. Insulin resistance in the brain is related to the progressive atrophy of the brain regions from initial progression of AD. These regions are cingulate cortices, medial temporal lobe, prefrontal gyri and other regions.³ Thus, there is an inhibition of the mechanisms of beta-amyloid removal, leading to its accumulation, which generates neuroinflammation, that in turn potentiates insulin resistance in the central nervous system, contributing to the genesis and progression of cognitive damage.2,3 Conclusions: Insulin resistance plays a major role in the initiation and perpetuation of cognitive impairment in AD. Furthermore, the components of the MS associated with AD, when treated with preventive and therapeutic measures, break this association by promoting rebalancing of the metabolism.

scholarly journals A meta-analysis of brain DNA methylation across sex, age and Alzheimer’s disease points for accelerated epigenetic aging in neurodegeneration

2020 ◽  
Author(s):  
C Pellegrini ◽  
C Pirazzini ◽  
C Sala ◽  
L Sambati ◽  
I Yusipov ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Methylation ◽  
Meta Analysis ◽  
Brain Regions ◽  
Epigenetic Aging ◽  
High Concordance ◽  
Males And Females ◽  
Cortical Regions ◽  
The Brain

AbstractAlzheimer’s disease (AD) is characterized by specific alterations of brain DNA methylation (DNAm) patterns. Age and sex, two major risk factors for AD, are also known to largely affect the epigenetic profiles in the brain, but their contribution to AD-associated DNAm changes has been poorly investigated. In this study we considered publicly available DNAm datasets of 4 brain regions (temporal, frontal, entorhinal cortex and cerebellum) from healthy adult subjects and AD patients, and performed a meta-analysis to identify sex-, age- and AD-associated epigenetic profiles. We showed that DNAm differences between males and females tend to be shared between the 4 brain regions, while aging differently affects cortical regions compared to cerebellum. We found that the proportion of sex-dependent probes whose methylation changes also during aging is higher than expected, but that differences between males and females tend to be maintained, with only few probes showing sex-by-age interaction. We did not find significant overlaps between AD- and sex-associated probes, nor disease-by-sex interaction effects. On the contrary, we found that AD-related epigenetic modifications are significantly enriched in probes whose DNAm changes with age and that there is a high concordance between the direction of changes (hyper or hypo-methylation) in aging and AD, supporting accelerated epigenetic aging in the disease.In conclusion, we demonstrated that age-associated, but not sex-associated DNAm concurs to the epigenetic deregulation observed in AD, providing new insight on how advanced age enables neurodegeneration.

scholarly journals Brain CHID1 Expression Correlates with NRGN and CALB1 in Healthy Subjects and AD Patients

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 882
Author(s):  
Paola Castrogiovanni ◽  
Cristina Sanfilippo ◽  
Rosa Imbesi ◽  
Grazia Maugeri ◽  
Debora Lo Furno ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Calcium Binding ◽  
Meta Analysis ◽  
Inverse Correlation ◽  
Brain Regions ◽  
Brain Disorder ◽  
Expression Levels ◽  
Healthy Control ◽  
The Brain

Alzheimer’s disease is a progressive, devastating, and irreversible brain disorder that, day by day, destroys memory skills and social behavior. Despite this, the number of known genes suitable for discriminating between AD patients is insufficient. Among the genes potentially involved in the development of AD, there are the chitinase-like proteins (CLPs) CHI3L1, CHI3L2, and CHID1. The genes of the first two have been extensively investigated while, on the contrary, little information is available on CHID1. In this manuscript, we conducted transcriptome meta-analysis on an extensive sample of brains of healthy control subjects (n = 1849) (NDHC) and brains of AD patients (n = 1170) in order to demonstrate CHID1 involvement. Our analysis revealed an inverse correlation between the brain CHID1 expression levels and the age of NDHC subjects. Significant differences were highlighted comparing CHID1 expression of NDHC subjects and AD patients. Exclusive in AD patients, the CHID1 expression levels were correlated positively to calcium-binding adapter molecule 1 (IBA1) levels. Furthermore, both in NDHC and in AD patient’s brains, the CHID1 expression levels were directly correlated with calbindin 1 (CALB1) and neurogranin (NRGN). According to brain regions, correlation differences were shown between the expression levels of CHID1 in prefrontal, frontal, occipital, cerebellum, temporal, and limbic system. Sex-related differences were only highlighted in NDHC. CHID1 represents a new chitinase potentially involved in the principal processes underlying Alzheimer’s disease.

Role of Nanomedicines in Delivery of Anti-Acetylcholinesterase Compounds to the Brain in Alzheimer’s Disease

2014 ◽  
Vol 13 (8) ◽  
pp. 1315-1324 ◽  
Author(s):  
Mohammad Ahmad ◽  
Javed Ahmad ◽  
Saima Amin ◽  
Mahfoozur Rahman ◽  
Mohammad Anwar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
The Brain

scholarly journals Deep-MEG: spatiotemporal CNN features and multiband ensemble classification for predicting the early signs of Alzheimer’s disease with magnetoencephalography

2021 ◽  
Author(s):  
Antonio Giovannetti ◽  
Gianluca Susi ◽  
Paola Casti ◽  
Arianna Mencattini ◽  
Sandra Pusil ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Regions ◽  
Ensemble Classification ◽  
The Novel ◽  
Ensemble Classifiers ◽  
Deep Convolutional Neural Networks ◽  
Early Signs ◽  
Data Representations ◽  
The Brain

AbstractIn this paper, we present the novel Deep-MEG approach in which image-based representations of magnetoencephalography (MEG) data are combined with ensemble classifiers based on deep convolutional neural networks. For the scope of predicting the early signs of Alzheimer’s disease (AD), functional connectivity (FC) measures between the brain bio-magnetic signals originated from spatially separated brain regions are used as MEG data representations for the analysis. After stacking the FC indicators relative to different frequency bands into multiple images, a deep transfer learning model is used to extract different sets of deep features and to derive improved classification ensembles. The proposed Deep-MEG architectures were tested on a set of resting-state MEG recordings and their corresponding magnetic resonance imaging scans, from a longitudinal study involving 87 subjects. Accuracy values of 89% and 87% were obtained, respectively, for the early prediction of AD conversion in a sample of 54 mild cognitive impairment subjects and in a sample of 87 subjects, including 33 healthy controls. These results indicate that the proposed Deep-MEG approach is a powerful tool for detecting early alterations in the spectral–temporal connectivity profiles and in their spatial relationships.

scholarly journals Peptides Derived from Growth Factors to Treat Alzheimer’s Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 6071
Author(s):  
Suzanne Gascon ◽  
Jessica Jann ◽  
Chloé Langlois-Blais ◽  
Mélanie Plourde ◽  
Christine Lavoie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Growth Factors ◽  
Signaling Pathways ◽  
Brain Structures ◽  
Therapeutic Strategies ◽  
Native Proteins ◽  
Receptor Sites ◽  
The Brain

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.

scholarly journals Alzheimer’s Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia

2021 ◽  
Vol 22 (7) ◽  
pp. 3330
Author(s):  
Mehdi Eshraghi ◽  
Aida Adlimoghaddam ◽  
Amir Mahmoodzadeh ◽  
Farzaneh Sharifzad ◽  
Hamed Yasavoli-Sharahi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Target ◽  
Neurological Disorder ◽  
Inflammatory Cells ◽  
Disease Pathogenesis ◽  
Current Review ◽  
The Brain ◽  
Comprehensive Discussion

Alzheimer’s disease (AD) is a debilitating neurological disorder, and currently, there is no cure for it. Several pathologic alterations have been described in the brain of AD patients, but the ultimate causative mechanisms of AD are still elusive. The classic hallmarks of AD, including am-yloid plaques (Aβ) and tau tangles (tau), are the most studied features of AD. Unfortunately, all the efforts targeting these pathologies have failed to show the desired efficacy in AD patients so far. Neuroinflammation and impaired autophagy are two other main known pathologies in AD. It has been reported that these pathologies exist in AD brain long before the emergence of any clinical manifestation of AD. Microglia are the main inflammatory cells in the brain and are considered by many researchers as the next hope for finding a viable therapeutic target in AD. Interestingly, it appears that the autophagy and mitophagy are also changed in these cells in AD. Inside the cells, autophagy and inflammation interact in a bidirectional manner. In the current review, we briefly discussed an overview on autophagy and mitophagy in AD and then provided a comprehensive discussion on the role of these pathways in microglia and their involvement in AD pathogenesis.

scholarly journals Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Angela M. Crist ◽  
Kelly M. Hinkle ◽  
Xue Wang ◽  
Christina M. Moloney ◽  
Billie J. Matchett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Digital Pathology ◽  
Selective Vulnerability ◽  
Brain Regions ◽  
Biochemical Analyses ◽  
The Brain ◽  
Relevant Gene ◽  
Tau Expression

AbstractSelective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer’s disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression.

Neuroinflammatory Signaling in the Pathogenesis of Alzheimer’s Disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Md. Sahab Uddin ◽  
Md. Tanvir Kabir ◽  
Maroua Jalouli ◽  
Md. Ataur Rahman ◽  
Philippe Jeandet ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immune ◽  
Misfolded Proteins ◽  
Inflammatory Signaling ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Immunological Mechanisms ◽  
The Brain

: Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the formation of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques. Growing evidence has suggested that AD pathogenesis is not only limited to the neuronal compartment but also strongly interacts with immunological processes in the brain. On the other hand, aggregated and misfolded proteins can bind with pattern recognition receptors located on astroglia and microglia and can in turn induce an innate immune response, characterized by the release of inflammatory mediators, ultimately playing a role in both the severity and the progression of the disease. It has been reported by genome-wide analysis that several genes which elevate the risk for sporadic AD encode for factors controlling the inflammatory response and glial clearance of misfolded proteins. Obesity and systemic inflammation are examples of external factors which may interfere with the immunological mechanisms of the brain and can induce disease progression. In this review, we discussed the mechanisms and essential role of inflammatory signaling pathways in AD pathogenesis. Indeed, interfering with immune processes and modulation of risk factors may lead to future therapeutic or preventive AD approaches.

Intranasal administration of mitochondria improves spatial memory in olfactory bulbectomized mice

2021 ◽  
pp. 153537022110568
Author(s):  
Natalia V Bobkova ◽  
Daria Y Zhdanova ◽  
Natalia V Belosludtseva ◽  
Nikita V Penkov ◽  
Galina D Mironova
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spatial Memory ◽  
Intranasal Administration ◽  
Brain Structures ◽  
Brain Regions ◽  
Dependent Manner ◽  
Behavioral Experiments ◽  
Hippocampal Cell Culture ◽  
The Brain

Here, we found that functionally active mitochondria isolated from the brain of NMRI donor mice and administrated intranasally to recipient mice penetrated the brain structures in a dose-dependent manner. The injected mitochondria labeled with the MitoTracker Red localized in different brain regions, including the neocortex and hippocampus, which are responsible for memory and affected by degeneration in patients with Alzheimer's disease. In behavioral experiments, intranasal microinjections of brain mitochondria of native NMRI mice improved spatial memory in the olfactory bulbectomized (OBX) mice with Alzheimer’s type degeneration. Control OBX mice demonstrated loss of spatial memory tested in the Morris water maze. Immunocytochemical analysis revealed that allogeneic mitochondria colocalized with the markers of astrocytes and neurons in hippocampal cell culture. The results suggest that a non-invasive route intranasal administration of mitochondria may be a promising approach to the treatment of neurodegenerative diseases characterized, like Alzheimer's disease, by mitochondrial dysfunction.

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