scholarly journals Exosomal miRNAs as Potential Diagnostic Biomarkers in Alzheimer’s Disease

2020 ◽  
Vol 13 (9) ◽  
pp. 243
Author(s):  
Ida Manna ◽  
Selene De Benedittis ◽  
Andrea Quattrone ◽  
Domenico Maisano ◽  
Enrico Iaccino ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Types ◽  
Bioactive Molecules ◽  
Clinical Value ◽  
Rna Sequences ◽  
Exosomal Mirnas ◽  
Preclinical And Clinical Studies ◽  
Internal And External Factors ◽  
Different Cell Types

Alzheimer’s disease (AD), a neurodegenerative disease, is linked to a variety of internal and external factors present from the early stages of the disease. There are several risk factors related to the pathogenesis of AD, among these exosomes and microRNAs (miRNAs) are of particular importance. Exosomes are nanocarriers released from many different cell types, including neuronal cells. Through the transfer of bioactive molecules, they play an important role both in the maintenance of physiological and in pathological conditions. Exosomes could be carriers of potential biomarkers useful for the assessment of disease progression and for therapeutic applications. miRNAs are small noncoding endogenous RNA sequences active in the regulation of protein expression, and alteration of miRNA expression can result in a dysregulation of key genes and pathways that contribute to disease development. Indeed, the involvement of exosomal miRNAs has been highlighted in various neurodegenerative diseases, and this opens the possibility that dysregulated exosomal miRNA profiles may influence AD disease. The advances in exosome-related biomarker detection in AD are summarized. Finally, in this review, we highlight the use of exosomal miRNAs as essential biomarkers in preclinical and clinical studies in Alzheimer’s disease, also taking a look at their potential clinical value.

Calcium signalling remodelling and disease

2012 ◽  
Vol 40 (2) ◽  
pp. 297-309 ◽  
Author(s):  
Michael J. Berridge
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bipolar Disorder ◽  
Cardiac Disease ◽  
Calcium Signalling ◽  
Cell Types ◽  
Wide Range ◽  
Inositol 1,4,5 Trisphosphate ◽  
Different Cell Types ◽  
Signalling Systems

A wide range of Ca2+ signalling systems deliver the spatial and temporal Ca2+ signals necessary to control the specific functions of different cell types. Release of Ca2+ by InsP3 (inositol 1,4,5-trisphosphate) plays a central role in many of these signalling systems. Ongoing transcriptional processes maintain the integrity and stability of these cell-specific signalling systems. However, these homoeostatic systems are highly plastic and can undergo a process of phenotypic remodelling, resulting in the Ca2+ signals being set either too high or too low. Such subtle dysregulation of Ca2+ signals have been linked to some of the major diseases in humans such as cardiac disease, schizophrenia, bipolar disorder and Alzheimer's disease.

The Blood brain-barrier and its role in Alzheimer’s disease

Neuroforum ◽  
2018 ◽  
Vol 24 (4) ◽  
pp. A197-A205 ◽  
Author(s):  
Steffen E. Storck ◽  
Claus U. Pietrzik
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Cell Types ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Different Cell Types ◽  
The Brain ◽  
Brain Homeostasis

Abstract The blood brain-barrier (BBB), built up by the interaction of different cell types in vessels of the brain, is essential for brain homeostasis. As a gatekeeper of the central nervous system (CNS), the BBB controls the exchange of molecules between brain and blood. In many neurodegenerative diseases including Alzheimer’s disease (AD) the BBB show alterations which impair brain function and promote neurodegeneration. As an important elimination route for neurotoxic amyloid-beta (Aβ), the BBB is crucial for the healthy brain by regulating the concentration of soluble Aβ in the interstitial fluid (ISF) in the brain. Here, we discuss the composition and distinctive physiological features of CNS vasculature and the pathological alterations that are present in AD and disturb BBB function.

scholarly journals Multi-cellular communities are perturbed in the aging human brain and with Alzheimer’s disease

2020 ◽  
Author(s):  
Anael Cain ◽  
Mariko Taga ◽  
Cristin McCabe ◽  
Idan Hekselman ◽  
Charles C. White ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Cell Types ◽  
Clinicopathologic Characteristics ◽  
Cellular Environment ◽  
Single Nucleus ◽  
Open Question ◽  
Different Cell Types

AbstractThe role of different cell types and their interactions in Alzheimer’s disease (AD) is an open question that we have pursued by mapping the human brain at the single cell level. Here, we present a high resolution cellular map of the aging frontal cortex by single nucleus RNA-sequencing of 24 individuals with different clinicopathologic characteristics; which we used to infer the cellular architecture of 640 individuals from bulk RNA-seq profiles. Powered by this sample of sufficient size to obtain statistically robust results, we uncovered AD associations with neuronal subtypes and oligodendroglial states. Moreover, we uncovered a network of cellular communities, each composed of different neuronal, glial and endothelial cells subpopulations whose frequencies are correlated across individuals. Two of the cellular communities are altered in relation to cognitive decline and tau pathology. Our work provides a roadmap for evaluating cross-cell type differences in the cellular environment of the AD brain.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

scholarly journals Effects of Gut Metabolites and Microbiota in Healthy and Marginal Livers Submitted to Surgery

2020 ◽  
Vol 22 (1) ◽  
pp. 44
Author(s):  
Marc Micó-Carnero ◽  
Carlos Rojano-Alfonso ◽  
Ana Isabel Álvarez-Mercado ◽  
Jordi Gracia-Sancho ◽  
Araní Casillas-Ramírez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Types ◽  
Microbial Populations ◽  
Operative Outcomes ◽  
Bidirectional Relationship ◽  
Preclinical And Clinical Studies ◽  
Different Cell Types ◽  
Stimulation Of

Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, its microbiota and the liver is referred to as the gut–liver axis. The translocation of bacterial products from the intestine to the liver induces inflammation in different cell types such as Kupffer cells, and a fibrotic response in hepatic stellate cells, resulting in deleterious effects on hepatocytes. Moreover, ischemia-reperfusion injury, a consequence of liver surgery, alters the microbiota profile, affecting inflammation, the immune response and even liver regeneration. Microbiota also seems to play an important role in post-operative outcomes (i.e., liver transplantation or liver resection). Nonetheless, studies to determine changes in the gut microbial populations produced during and after surgery, and affecting liver function and regeneration are scarce. In the present review we analyze and discuss the preclinical and clinical studies reported in the literature focused on the evaluation of alterations in microbiota and its products as well as their effects on post-operative outcomes in hepatic surgery.

scholarly journals Antioxidant strategies for Alzheimer's disease

2002 ◽  
Vol 61 (2) ◽  
pp. 191-202 ◽  
Author(s):  
Michael Grundman ◽  
Patrick Delaney
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vitamin E ◽  
Oxidative Damage ◽  
Functional Decline ◽  
Antioxidant Properties ◽  
Epidemiological Studies ◽  
Clinical Value ◽  
Antioxidant Defences ◽  
Ad Prevention

Oxidative damage is present within the brains of patients with Alzheimer's disease (AD), and is observed within every class of biomolecule, including nucleic acids, proteins, lipids and carbohydrates. Oxidative injury may develop secondary to excessive oxidative stress resulting from β-amyloid-induced free radicals, mitochondrial abnormalities, inadequate energy supply, inflammation or altered antioxidant defences. Treatment with antioxidants is a promising approach for slowing disease progression to the extent that oxidative damage may be responsible for the cognitive and functional decline observed in AD. Although not a uniformly consistent observation, a number of epidemiological studies have found a link between antioxidant intake and a reduced incidence of dementia, AD and cognitive decline in elderly populations. In AD clinical trials molecules with antioxidant properties such as vitamin E andGinkgo bilobaextract have shown modest benefit. A clinical trial with vitamin E is currently ongoing to determine if it can delay progression to AD in individuals with mild cognitive impairment. Combinations of antioxidants might be of even greater potential benefit for AD, especially if the agents worked in different cellular compartments or had complementary activity (e.g. vitamins E, C and ubiquinone). Naturally-occurring compounds with antioxidant capacity are available and widely marketed (e.g. vitamin C, ubiquinone, lipoic acid, β-carotene, creatine, melatonin, curcumin) and synthetic compounds are under development by industry. Nevertheless, the clinical value of these agents for AD prevention and treatment is ambiguous, and will remain so until properly designed human trials have been performed.

scholarly journals PET imaging of 18F-florbetapir in cognitively impaired individuals: Lack of activity within the cerebellar cortex

2018 ◽  
Vol 10 (3) ◽  
Author(s):  
Michael A. Meyer ◽  
Allison Caccia ◽  
Danielle Martinez ◽  
Mark A. Mingos
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Cerebellar Cortex ◽  
Pet Imaging ◽  
Parent Compound ◽  
Hepatic Metabolism ◽  
Subcortical White Matter ◽  
Clinical Value ◽  
Type Pattern

Ten individuals suspected of having possible Alzheimer disease underwent PET imaging using 18F-Flubetapir. Only one of ten individuals had a pattern typical for normal elderly control subjects with 9 of the 10 showing a Alzheimer type pattern for the cerebral cortex yet all 10 subjects had uniformly low to absent tracer localization to the cerebellar cortex; significantly high tracer activity was noted within the subcortical white matter of the cerebellum in a symmetric manner in all cases. In consideration of studies that have shown amyloid deposits within the cerebellar cortex in 90% of pathologically proven cases of Alzheimer’s disease, these findings raise questions about the actual clinical value of florbetapir PET imaging in evaluating cerebellar involvement and raises questions whether PET imaging of this tracer accurately portrays patterns of amyloid deposition, as there is rapid hepatic metabolism of the parent compound after intravenous injection. Possible links to Alzheimer’s disease related alterations in blood-brain barrier permeability to the parent compound and subsequent radiolabelled metabolites are discussed as potential mechanisms that could explain the associated localization of the tracer to the brainstem and subcortical white matter within the cerebrum and cerebellum of Alzheimer’s disease patients.

scholarly journals Antidiabetic Drugs in Alzheimer’s Disease: Mechanisms of Action and Future Perspectives

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Grazia Daniela Femminella ◽  
Leonardo Bencivenga ◽  
Laura Petraglia ◽  
Lucia Visaggi ◽  
Lucia Gioia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
The Elderly ◽  
Mechanisms Of Action ◽  
Antidiabetic Drugs ◽  
Common Mechanism ◽  
Public Health Burden ◽  
Preclinical And Clinical Studies ◽  
And Oxidative Stress ◽  
Potential Use

Diabetes mellitus (DM) and Alzheimer’s disease (AD) are two highly prevalent conditions in the elderly population and major public health burden. In the past decades, a pathophysiological link between DM and AD has emerged and central nervous system insulin resistance might play a significant role as a common mechanism; however, other factors such as inflammation and oxidative stress seem to contribute to the shared pathophysiological link. Both preclinical and clinical studies have evaluated the possible neuroprotective mechanisms of different classes of antidiabetic medications in AD, with some promising results. Here, we review the evidence on the mechanisms of action of antidiabetic drugs and their potential use in AD.

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