scholarly journals Circulating glutamine and Alzheimer’s disease: a Mendelian randomization study

2019 ◽  
Author(s):  
Charleen D. Adams
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Neurodegenerative Disorder ◽  
Glutamate Metabolism ◽  
Inverse Variance ◽  
The Brain ◽  
Metabolic Cycle

ABSTRACTINTRODUCTIONAlzheimer’s disease is a devastating neurodegenerative disorder. Its worldwide prevalence is over 24 million and is expected to double by 2040. Finding ways to prevent its cognitive decline is urgent.METHODSA two-sample Mendelian randomization study was performed instrumenting glutamine, which is abundant in blood, capable of crossing the blood-brain barrier, and involved in a metabolic cycle with glutamate in the brain.RESULTSThe results reveal a protective effect of circulating glutamine (inverse-variance weighted method, odds ratio per 1-SD increase in circulating glutamine = 0.83; 95% CI 0.71, 0.97; P = 0.02).CONCLUSIONThese findings lend credence to the emerging story supporting the modifiability of glutamine/glutamate metabolism for the prevention of cognitive decline. More circulating glutamine might mean that more substrate is available during times of stress, acting as a neuroprotectant. Modifications to exogenous glutamine may be worth exploring in future efforts to prevent and/or treat Alzheimer’s disease.

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 Intermittent Hypoxic Conditioning Rescues Cognition and Mitochondrial Bioenergetic Profile in the Triple Transgenic Mouse Model of Alzheimer’s Disease

2021 ◽  
Vol 22 (1) ◽  
pp. 461
Author(s):  
Sónia C. Correia ◽  
Nuno J. Machado ◽  
Marco G. Alves ◽  
Pedro F. Oliveira ◽  
Paula I. Moreira
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Brain Cortex ◽  
Neurodegenerative Disorder ◽  
Special Focus ◽  
Mitochondrial Bioenergetics ◽  
Related Phenotype ◽  
Brain Resilience ◽  
The Brain

The lack of effective disease-modifying therapeutics to tackle Alzheimer’s disease (AD) is unsettling considering the actual prevalence of this devastating neurodegenerative disorder worldwide. Intermittent hypoxic conditioning (IHC) is a powerful non-pharmacological procedure known to enhance brain resilience. In this context, the aim of the present study was to investigate the potential long-term protective impact of IHC against AD-related phenotype, putting a special focus on cognition and mitochondrial bioenergetics and dynamics. For this purpose, six-month-old male triple transgenic AD mice (3×Tg-AD) were submitted to an IHC protocol for two weeks and the behavioral assessment was performed at 8.5 months of age, while the sacrifice of mice occurred at nine months of age and their brains were removed for the remaining analyses. Interestingly, IHC was able to prevent anxiety-like behavior and memory and learning deficits and significantly reduced brain cortical levels of amyloid-β (Aβ) in 3×Tg-AD mice. Concerning brain energy metabolism, IHC caused a significant increase in brain cortical levels of glucose and a robust improvement of the mitochondrial bioenergetic profile in 3×Tg-AD mice, as mirrored by the significant increase in mitochondrial membrane potential (ΔΨm) and respiratory control ratio (RCR). Notably, the improvement of mitochondrial bioenergetics seems to result from an adaptative coordination of the distinct but intertwined aspects of the mitochondrial quality control axis. Particularly, our results indicate that IHC favors mitochondrial fusion and promotes mitochondrial biogenesis and transport and mitophagy in the brain cortex of 3×Tg-AD mice. Lastly, IHC also induced a marked reduction in synaptosomal-associated protein 25 kDa (SNAP-25) levels and a significant increase in both glutamate and GABA levels in the brain cortex of 3×Tg-AD mice, suggesting a remodeling of the synaptic microenvironment. Overall, these results demonstrate the effectiveness of the IHC paradigm in forestalling the AD-related phenotype in the 3×Tg-AD mouse model, offering new insights to AD therapy and forcing a rethink concerning the potential value of non-pharmacological interventions in clinical practice.

scholarly journals Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?

2016 ◽  
Vol 10 (3) ◽  
pp. 170-177 ◽  
Author(s):  
Adalberto Studart Neto ◽  
Ricardo Nitrini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Clinical Manifestation ◽  
Neurodegenerative Disorder ◽  
Subjective Cognitive Decline ◽  
Subjective Memory ◽  
Increased Risk

ABSTRACT Background: Mild cognitive impairment is considered as the first clinical manifestation of Alzheimer's disease (AD), when the individual exhibits below performance on standardized neuropsychological tests. However, some subjects before having a lower performance on cognitive assessments already have a subjective memory complaint. Objective: A review about subjective cognitive decline, the association with AD biomarkers and risk of conversion to dementia. Methods: We performed a comprehensive non-systematic review on PubMed. The keywords used in the search were terms related to subjective cognitive decline. Results: Subjective cognitive decline is characterized by self-experience of deterioration in cognitive performance not detected objectively through formal neuropsychological testing. However, various terms and definitions have been used in the literature and the lack of a widely accepted concept hampers comparison of studies. Epidemiological data have shown that individuals with subjective cognitive decline are at increased risk of progression to AD dementia. In addition, there is evidence that this group has a higher prevalence of positive biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is not the only cause of subjective cognitive decline and various other conditions can be associated with subjective memory complaints, such as psychiatric disorders or normal aging. The features suggestive of a neurodegenerative disorder are: onset of decline within the last five years, age at onset above 60 years, associated concerns about decline and confirmation by an informant. Conclusion: These findings support the idea that subjective cognitive complaints may be an early clinical marker that precedes mild cognitive impairment due to Alzheimer's disease.

scholarly journals Immunosenescence of Natural Killer Cells, Inflammation, and Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Corona Solana ◽  
Raquel Tarazona ◽  
Rafael Solana
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Lymphoid Cells ◽  
Target Cells ◽  
The Brain

Alzheimer’s disease (AD) represents the most common cause of dementia in the elderly. AD is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Although the aetiology of AD is not clear, both environmental factors and heritable predisposition may contribute to disease occurrence. In addition, inflammation and immune system alterations have been linked to AD. The prevailing hypothesis as cause of AD is the deposition in the brain of amyloid beta peptides (Aβ). Although Aβ have a role in defending the brain against infections, their accumulation promotes an inflammatory response mediated by microglia and astrocytes. The production of proinflammatory cytokines and other inflammatory mediators such as prostaglandins and complement factors favours the recruitment of peripheral immune cells further promoting neuroinflammation. Age-related inflammation and chronic infection with herpes virus such as cytomegalovirus may also contribute to inflammation in AD patients. Natural killer (NK) cells are innate lymphoid cells involved in host defence against viral infections and tumours. Once activated NK cells secrete cytokines such as IFN-γ and TNF-α and chemokines and exert cytotoxic activity against target cells. In the elderly, changes in NK cell compartment have been described which may contribute to the lower capacity of elderly individuals to respond to pathogens and tumours. Recently, the role of NK cells in the immunopathogenesis of AD is discussed. Although in AD patients the frequency of NK cells is not affected, a high NK cell response to cytokines has been described together with NK cell dysregulation of signalling pathways which is in part involved in this altered behaviour.

Graph Theory-Based Brain Network Connectivity Analysis and Classification of Alzheimer’s Disease

2021 ◽  
Author(s):  
A. Thushara ◽  
C. Ushadevi Amma ◽  
Ansamma John
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Graph Theory ◽  
Neurodegenerative Disorder ◽  
Brain Networks ◽  
Network Connectivity ◽  
Brain Regions ◽  
Brain Network ◽  
Fiber Tracts ◽  
The Brain

Alzheimer’s Disease (AD) is basically a progressive neurodegenerative disorder associated with abnormal brain networks that affect millions of elderly people and degrades their quality of life. The abnormalities in brain networks are due to the disruption of White Matter (WM) fiber tracts that connect the brain regions. Diffusion-Weighted Imaging (DWI) captures the brain’s WM integrity. Here, the correlation betwixt the WM degeneration and also AD is investigated by utilizing graph theory as well as Machine Learning (ML) algorithms. By using the DW image obtained from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, the brain graph of each subject is constructed. The features extracted from the brain graph form the basis to differentiate between Mild Cognitive Impairment (MCI), Control Normal (CN) and AD subjects. Performance evaluation is done using binary and multiclass classification algorithms and obtained an accuracy that outperforms the current top-notch DWI-based studies.

scholarly journals Impact of Physical Activity on Cognitive Decline, Dementia, and Its Subtypes: Meta-Analysis of Prospective Studies

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Chris B. Guure ◽  
Noor A. Ibrahim ◽  
Mohd B. Adam ◽  
Salmiah Md Said
Keyword(s):  
Physical Activity ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protective Effect ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Prospective Studies ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Nonparametric Models

The association of physical activity with dementia and its subtypes has remained controversial in the literature and has continued to be a subject of debate among researchers. A systematic review and meta-analysis of longitudinal studies on the relationship between physical activity and the risk of cognitive decline, all-cause dementia, Alzheimer’s disease, and vascular dementia among nondemented subjects are considered. A comprehensive literature search in all available databases was conducted up until April 2016. Well-defined inclusion and exclusion criteria were developed with focus on prospective studies ≥ 12 months. The overall sample from all studies is 117410 with the highest follow-up of 28 years. The analyses are performed with both Bayesian parametric and nonparametric models. Our analysis reveals a protective effect for high physical activity on all-cause dementia, odds ratio of 0.79, 95% CI (0.69, 0.88), a higher and better protective effect for Alzheimer’s disease, odds ratio of 0.62, 95% CI (0.49, 0.75), cognitive decline odds ratio of 0.67, 95% CI (0.55, 0.78), and a nonprotective effect for vascular dementia of 0.92, 95% CI (0.62, 1.30). Our findings suggest that physical activity is more protective against Alzheimer’s disease than it is for all-cause dementia, vascular dementia, and cognitive decline.

scholarly journals Pleiotropic Protective Effects of Phytochemicals in Alzheimer's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Sergio Davinelli ◽  
Nadia Sapere ◽  
Davide Zella ◽  
Renata Bracale ◽  
Mariano Intrieri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Protective Effects ◽  
Drug Candidates ◽  
Molecular Events ◽  
Therapeutic Value ◽  
Phytochemical Compounds ◽  
Multiple Levels ◽  
The Brain

Alzheimer’s disease (AD) is a severe chronic neurodegenerative disorder of the brain characterised by progressive impairment in memory and cognition. In the past years an intense research has aimed at dissecting the molecular events of AD. However, there is not an exhaustive knowledge about AD pathogenesis and a limited number of therapeutic options are available to treat this neurodegenerative disease. Consequently, considering the heterogeneity of AD, therapeutic agents acting on multiple levels of the pathology are needed. Recent findings suggest that phytochemicals compounds with neuroprotective features may be an important resources in the discovery of drug candidates against AD. In this paper we will describe some polyphenols and we will discuss their potential role as neuroprotective agents. Specifically, curcumin, catechins, and resveratrol beyond their antioxidant activity are also involved in antiamyloidogenic and anti-inflammatory mechanisms. We will focus on specific molecular targets of these selected phytochemical compounds highlighting the correlations between their neuroprotective functions and their potential therapeutic value in AD.

scholarly journals Cognitive and Disease-Modifying Effects of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibition in Male Tg2576 Mice, a Model of Alzheimer's Disease

Endocrinology ◽  
2015 ◽  
Vol 156 (12) ◽  
pp. 4592-4603 ◽  
Author(s):  
Karen Sooy ◽  
June Noble ◽  
Andrew McBride ◽  
Margaret Binnie ◽  
Joyce L. W. Yau ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Hydroxysteroid Dehydrogenase ◽  
Insulin Degrading Enzyme ◽  
Short Term Treatment ◽  
Model Of Alzheimer’S Disease ◽  
The Brain ◽  
Tg2576 Mice

Chronic exposure to elevated levels of glucocorticoids has been linked to age-related cognitive decline and may play a role in Alzheimer's disease. In the brain, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies intracellular glucocorticoid levels. We show that short-term treatment of aged, cognitively impaired C57BL/6 mice with the potent and selective 11β-HSD1 inhibitor UE2316 improves memory, including after intracerebroventricular drug administration to the central nervous system alone. In the Tg2576 mouse model of Alzheimer's disease, UE2316 treatment of mice aged 14 months for 4 weeks also decreased the number of β-amyloid (Aβ) plaques in the cerebral cortex, associated with a selective increase in local insulin-degrading enzyme (involved in Aβ breakdown and known to be glucocorticoid regulated). Chronic treatment of young Tg2576 mice with UE2316 for up to 13 months prevented cognitive decline but did not prevent Aβ plaque formation. We conclude that reducing glucocorticoid regeneration in the brain improves cognition independently of reduced Aβ plaque pathology and that 11β-HSD1 inhibitors have potential as cognitive enhancers in age-associated memory impairment and Alzheimer's dementia.

scholarly journals Impact of Tau on Neurovascular Pathology in Alzheimer's Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Elisa Canepa ◽  
Silvia Fossati
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Neurovascular Unit ◽  
Amyloid Angiopathy ◽  
Brain Vasculature ◽  
Mitochondrial Alterations ◽  
Species Production ◽  
The Impact ◽  
The Brain

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most prevalent cause of dementia. The main cerebral histological hallmarks are represented by parenchymal insoluble deposits of amyloid beta (Aβ plaques) and neurofibrillary tangles (NFT), intracellular filamentous inclusions of tau, a microtubule-associated protein. It is well-established that cerebrovascular dysfunction is an early feature of AD pathology, but the detrimental mechanisms leading to blood vessel impairment and the associated neurovascular deregulation are not fully understood. In 90% of AD cases, Aβ deposition around the brain vasculature, known as cerebral amyloid angiopathy (CAA), alters blood brain barrier (BBB) essential functions. While the effects of vascular Aβ accumulation are better documented, the scientific community has only recently started to consider the impact of tau on neurovascular pathology in AD. Emerging compelling evidence points to transmission of neuronal tau to different brain cells, including astrocytes, as well as to the release of tau into brain interstitial fluids, which may lead to perivascular neurofibrillar tau accumulation and toxicity, affecting vessel architecture, cerebral blood flow (CBF), and vascular permeability. BBB integrity and functionality may therefore be impacted by pathological tau, consequentially accelerating the progression of the disease. Tau aggregates have also been shown to induce mitochondrial damage: it is known that tau impairs mitochondrial localization, distribution and dynamics, alters ATP and reactive oxygen species production, and compromises oxidative phosphorylation systems. In light of this previous knowledge, we postulate that tau can initiate neurovascular pathology in AD through mitochondrial dysregulation. In this review, we will explore the literature investigating tau pathology contribution to the malfunction of the brain vasculature and neurovascular unit, and its association with mitochondrial alterations and caspase activation, in cellular, animal, and human studies of AD and tauopathies.

scholarly journals The Potential Benefits of Nanotechnology in Treating Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Tan Sook Ling ◽  
Shanthini Chandrasegaran ◽  
Low Zhi Xuan ◽  
Tong Li Suan ◽  
Elaine Elaine ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Amyloid Plaques ◽  
Disease Diagnosis ◽  
Drug Bioavailability ◽  
Potential Toxicity ◽  
Alternative Approach ◽  
Potential Benefits ◽  
The Brain

Alzheimer’s disease is a neurodegenerative disorder that is caused by the accumulation of beta-amyloid plaques in the brain. Currently, there is no definitive cure available to treat Alzheimer’s disease. The available medication in the market has the ability to only slow down its progression. However, nanotechnology has shown its superiority that can be applied for medical usage and it has a great potential in the therapy of Alzheimer’s disease, specifically in the disease diagnosis and providing an alternative approach to treat Alzheimer’s disease. This is done by increasing the efficiency of drug delivery by penetrating and overcoming the blood-brain barrier. Having said that, there are limitations that need to be further investigated and researched in order to minimize the adverse effects and potential toxicity and to improve drug bioavailability. The recent advances in the treatment of Alzheimer’s disease using nanotechnology include the regeneration of stem cells, nanomedicine, and neuroprotection. In this review, we will discuss the advancement of nanotechnology which helps in the diagnosis and treatment of neurodegenerative disorders such as Alzheimer’s disease as well as its challenges.

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