scholarly journals Brain, immune system and selenium: a starting point for a new diagnostic marker for Alzheimer’s disease?

2018 ◽  
Vol 138 (4) ◽  
pp. 223-226 ◽  
Author(s):  
Cesare Achilli ◽  
Annarita Ciana ◽  
Giampaolo Minetti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Blood Cells ◽  
Senile Dementia ◽  
Imaging Techniques ◽  
Normal Subjects ◽  
Methionine Sulfoxide Reductase ◽  
Neutrophil Granulocytes ◽  
Starting Point

The clinical diagnosis of Alzheimer’s disease (AD) is based primarily on neuropsychological tests, which assess the involutive damage, and imaging techniques that evaluate morphologic changes in the brain. Currently available diagnostic tests do not show complete specificity and do not permit accurate differentiation between AD and other forms of senile dementia. The correlation of these tests with laboratory investigations based on biochemical parameters could increase the certainty of diagnosis. In recent years, several biochemical markers for the diagnosis of AD have been proposed, but in most cases they show a limited specificity and their application is invasive, requiring, in general, sampling of cerebrospinal fluid. Thus, the use of a peripheral biochemical marker could represent a valuable complement for the diagnosis of this disease. Several studies have shown a relationship between neurodegenerative disorders typical of the ageing process, weakening of the immune system and alterations in the levels of selenium and of the antioxidant selenoenzymes in brain tissues and blood cells. Among blood cells, neutrophil granulocytes uniquely express the selenoenzyme methionine sulfoxide reductase B1 (MsrB1). In a preliminary analysis carried out on neutrophils from subjects affected by AD, we observed a significant decline in MsrB1 activity compared to normal subjects. Therefore, we deem it of particular interest to explore the potential use of MsrB1 as a selective peripheral marker for the diagnosis of AD.

scholarly journals Brain, immune system and selenium: a starting point for a new diagnostic marker for Alzheimer’s disease?

2017 ◽  
Author(s):  
Cesare Achilli ◽  
Annarita Ciana ◽  
Giampaolo Minetti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Senile Dementia ◽  
Pathological Condition ◽  
Imaging Techniques ◽  
Clinical Parameter ◽  
Neutrophil Granulocytes ◽  
Starting Point ◽  
Valuable Complement

AbstractThe clinical diagnosis of Alzheimer’s disease (AD) is based primarily on neuropsychological tests, which assess the involutive damage, and imaging techniques that evaluate morphologic changes in the brain. The currently available diagnostic tests do not show complete specificity and do not permit an accurate differentiation between AD and other forms of senile dementia. The correlation of these tests with laboratory investigations based on biochemical parameters could increase the certainty of the diagnosis. In recent years, several biochemical markers for the diagnosis of AD have been proposed, but in most cases they show a limited specificity and their application is invasive, because it generally requires the sampling of cerebrospinal fluid. Therefore, the use of a peripheral biochemical marker could represent a valuable complement for the diagnosis of this disease.Several studies have shown a relationship between the neurodegenerative disorders typical of the ageing process, the weakening of the immune system, alterations in the levels of selenium and of the antioxidant selenoenzymes in brain tissues and blood cells, particularly in neutrophil granulocytes. The levels of peripheral selenoenzymes may reveal a promising clinical parameter for helping in the assessment of the pathological condition in AD.HighlightsMsrBl is one of the 25 selenoenzymes expressed in the humansMsrBl is highly expressed in human circulating neutrophilsThe diagnostic markers for Alzheimer’s disease are still insufficiently validatedThe impairment of some selenoenzymes is associated with Alzheimer’s diseaseNeutrophil MsrBl can be a peripheral marker for the diagnosis of Alzheimer’s disease

scholarly journals Brain Aging and Alzheimer's Disease*

1978 ◽  
Vol 23 (4) ◽  
pp. 229-233 ◽  
Author(s):  
D.R. Crapper ◽  
U. Deboni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Brain Aging ◽  
Senile Dementia ◽  
Pathological Process ◽  
Alzheimer Type ◽  
Neurotoxic Effect ◽  
Presenile Dementia ◽  
Common Cause

The most common cause of senile dementia appears to be a pathological process indistinguishable from that found in presenile dementia of the Alzheimer type. Consideration of the neuropathological changes suggest that this disease may involve the interaction of at least three processes: a viral-like infection, a disorder in the immune system and the neurotoxic effect of an environmental agent. The evidence in support of this hypothesis is reviewed.

scholarly journals The Model of Aging Acceleration Network Reveals the Correlation of Alzheimer’s Disease and Aging at System Level

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Mengyu Zhou ◽  
Xiaoqiong Xia ◽  
Hao Yan ◽  
Sijia Li ◽  
Shiyu Bian ◽  
...  
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Biological Networks ◽  
Senile Dementia ◽  
Accelerated Aging ◽  
Machine Learning Techniques ◽  
System Level ◽  
Learning Techniques

As the incidence of senile dementia continues to increase, researches on Alzheimer’s disease (AD) have become more and more important. Several studies have reported that there is a close relationship between AD and aging. Some researchers even pointed out that if we wanted to understand AD in depth, mechanisms of AD based on accelerated aging must be studied. Nowadays, machine learning techniques have been utilized to deal with large and complex profiles, thus playing an important role in disease researches (i.e., modelling biological systems, identifying key modules based on biological networks, and so on). Here, we developed an aging predictor and an AD predictor using machine learning techniques, respectively. Both aging and AD biomarkers were identified to provide insights into genes associated with AD. Besides, aging scores were calculated to reflect the aging process of brain tissues. As a result, the aging acceleration network and the aging-AD bipartite graph were constructed to delve into the relationship between AD and aging. Finally, a series of network and enrichment analyses were also conducted to gain further insights into the mechanisms of AD based on accelerated aging. In a word, our results indicated that aging may contribute to the development of AD by affecting the function of the immune system and the energy metabolism process, where the immune system may play a more prominent role in AD.

Consideration of a Pharmacological Combinatorial Approach to Inhibit Chronic Inflammation in Alzheimer’s Disease

2019 ◽  
Vol 16 (11) ◽  
pp. 1007-1017 ◽  
Author(s):  
James G. McLarnon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Chronic Inflammation ◽  
Preventive Strategy ◽  
Subsequent Work ◽  
Activated Microglia ◽  
Starting Point ◽  
Anti Inflammatory ◽  
Cocktail Approach

A combinatorial cocktail approach is suggested as a rationale intervention to attenuate chronic inflammation and confer neuroprotection in Alzheimer’s disease (AD). The requirement for an assemblage of pharmacological compounds follows from the host of pro-inflammatory pathways and mechanisms present in activated microglia in the disease process. This article suggests a starting point using four compounds which present some differential in anti-inflammatory targets and actions but a commonality in showing a finite permeability through Blood-brain Barrier (BBB). A basis for firstchoice compounds demonstrated neuroprotection in animal models (thalidomide and minocycline), clinical trial data showing some slowing in the progression of pathology in AD brain (ibuprofen) and indirect evidence for putative efficacy in blocking oxidative damage and chemotactic response mediated by activated microglia (dapsone). It is emphasized that a number of candidate compounds, other than ones suggested here, could be considered as components of the cocktail approach and would be expected to be examined in subsequent work. In this case, systematic testing in AD animal models is required to rigorously examine the efficacy of first-choice compounds and replace ones showing weaker effects. This protocol represents a practical approach to optimize the reduction of microglial-mediated chronic inflammation in AD pathology. Subsequent work would incorporate the anti-inflammatory cocktail delivery as an adjunctive treatment with ones independent of inflammation as an overall preventive strategy to slow the progression of AD.

Microglia in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 29-43 ◽  
Author(s):  
Patrick Süß ◽  
Johannes C.M. Schlachetzki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Amyloid Β ◽  
Disease Stage ◽  
Disease Modifying Therapy ◽  
Transcriptomic Signature

: Alzheimer’s Disease (AD) is the most frequent neurodegenerative disorder. Although proteinaceous aggregates of extracellular Amyloid-β (Aβ) and intracellular hyperphosphorylated microtubule- associated tau have long been identified as characteristic neuropathological hallmarks of AD, a disease- modifying therapy against these targets has not been successful. An emerging concept is that microglia, the innate immune cells of the brain, are major players in AD pathogenesis. Microglia are longlived tissue-resident professional phagocytes that survey and rapidly respond to changes in their microenvironment. Subpopulations of microglia cluster around Aβ plaques and adopt a transcriptomic signature specifically linked to neurodegeneration. A plethora of molecules and pathways associated with microglia function and dysfunction has been identified as important players in mediating neurodegeneration. However, whether microglia exert either beneficial or detrimental effects in AD pathology may depend on the disease stage. : In this review, we summarize the current knowledge about the stage-dependent role of microglia in AD, including recent insights from genetic and gene expression profiling studies as well as novel imaging techniques focusing on microglia in human AD pathology and AD mouse models.

scholarly journals Optical Imaging of Beta-Amyloid Plaques in Alzheimer’s Disease

Biosensors ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 255
Author(s):  
Ziyi Luo ◽  
Hao Xu ◽  
Liwei Liu ◽  
Tymish Y. Ohulchanskyy ◽  
Junle Qu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Optical Imaging ◽  
Imaging Techniques ◽  
High Sensitivity ◽  
Pathological Feature ◽  
Promising Tool ◽  
Abnormal Accumulation ◽  
Accumulation Mechanism ◽  
The Brain

Alzheimer’s disease (AD) is a multifactorial, irreversible, and incurable neurodegenerative disease. The main pathological feature of AD is the deposition of misfolded β-amyloid protein (Aβ) plaques in the brain. The abnormal accumulation of Aβ plaques leads to the loss of some neuron functions, further causing the neuron entanglement and the corresponding functional damage, which has a great impact on memory and cognitive functions. Hence, studying the accumulation mechanism of Aβ in the brain and its effect on other tissues is of great significance for the early diagnosis of AD. The current clinical studies of Aβ accumulation mainly rely on medical imaging techniques, which have some deficiencies in sensitivity and specificity. Optical imaging has recently become a research hotspot in the medical field and clinical applications, manifesting noninvasiveness, high sensitivity, absence of ionizing radiation, high contrast, and spatial resolution. Moreover, it is now emerging as a promising tool for the diagnosis and study of Aβ buildup. This review focuses on the application of the optical imaging technique for the determination of Aβ plaques in AD research. In addition, recent advances and key operational applications are discussed.

scholarly journals Identification of Novel Cathepsin B Inhibitors with Implications in Alzheimer’s Disease: Computational Refining and Biochemical Evaluation

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1946
Author(s):  
Nitin Chitranshi ◽  
Ashutosh Kumar ◽  
Samran Sheriff ◽  
Veer Gupta ◽  
Angela Godinez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hydrogen Bond ◽  
Virtual Screening ◽  
Cathepsin B ◽  
Amyloid Β ◽  
Proteolytic Degradation ◽  
Hydrogen Bond Acceptor ◽  
Starting Point ◽  
The Brain

Amyloid precursor protein (APP), upon proteolytic degradation, forms aggregates of amyloid β (Aβ) and plaques in the brain, which are pathological hallmarks of Alzheimer’s disease (AD). Cathepsin B is a cysteine protease enzyme that catalyzes the proteolytic degradation of APP in the brain. Thus, cathepsin B inhibition is a crucial therapeutic aspect for the discovery of new anti-Alzheimer’s drugs. In this study, we have employed mixed-feature ligand-based virtual screening (LBVS) by integrating pharmacophore mapping, docking, and molecular dynamics to detect small, potent molecules that act as cathepsin B inhibitors. The LBVS model was generated by using hydrophobic (HY), hydrogen bond acceptor (HBA), and hydrogen bond donor (HBD) features, using a dataset of 24 known cathepsin B inhibitors of both natural and synthetic origins. A validated eight-feature pharmacophore hypothesis (Hypo III) was utilized to screen the Maybridge chemical database. The docking score, MM-PBSA, and MM-GBSA methodology was applied to prioritize the lead compounds as virtual screening hits. These compounds share a common amide scaffold, and showed important interactions with Gln23, Cys29, His110, His111, Glu122, His199, and Trp221. The identified inhibitors were further evaluated for cathepsin-B-inhibitory activity. Our study suggests that pyridine, acetamide, and benzohydrazide compounds could be used as a starting point for the development of novel therapeutics.

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