scholarly journals Lipid Rafts and Development of Alzheimer’s Disease

2021 ◽  
Author(s):  
Mario Díaz ◽  
Raquel Marin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Rafts ◽  
Current Evidence ◽  
Amyloid Beta Peptides ◽  
Main Component ◽  
And Function ◽  
Human Brains ◽  
Neuronal Physiology ◽  
The Impact

A wealth of evidence accumulated over the last two decades has unambiguously linked lipid rafts to neurodegenerative diseases, in particular to Alzheimer’s disease (AD). These microdomains are highly dynamic membrane platforms with differentiated physicochemical and molecular properties compared to the surrounding membrane microenvironment, and are the locus for a number of central processes in neuronal physiology. Most recent evidence pinpoint to lipid rafts as main players in AD neuropathology. It is now widely accepted that lipid rafts actively participate in the processing of amyloid precursor protein to generate amyloid beta peptides, a main component of amyloid plaques. Current evidence have highlighted the existence of severe alterations in the molecular structure and functionality of lipid rafts in the frontal cortex of human brains affected by Alzheimer’s disease. An exceptionally interesting observation is that lipid raft destabilization can be demonstrated even at the earliest stages of AD neuropathology. In the present review, we will first elaborate on the structure and function of these multifaceted subcellular structures and second to focus on the impact of their alterations in neuronal pathophysiology along the onset and progression of AD continuum.

scholarly journals Astrocytic transporters in Alzheimer's disease

2017 ◽  
Vol 474 (3) ◽  
pp. 333-355 ◽  
Author(s):  
Chris Ugbode ◽  
Yuhan Hu ◽  
Benjamin Whalley ◽  
Chris Peers ◽  
Marcus Rattray ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Neurological Diseases ◽  
Current Evidence ◽  
Specific Targeting ◽  
Disease Modifying Therapies ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
And Function

Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both cellular and molecular changes at an early stage in neurological diseases, including Alzheimer's disease (AD). These changes may reflect a change from a neuroprotective to a neurotoxic phenotype. Given the lack of current disease-modifying therapies for AD, astrocytes have become an interesting and viable target for therapeutic intervention. The astrocyte transport system covers a diverse array of proteins involved in metabolic support, neurotransmission and synaptic architecture. Therefore, specific targeting of individual transporter families has the potential to suppress neurodegeneration, a characteristic hallmark of AD. A small number of the 400 transporter superfamilies are expressed in astrocytes, with evidence highlighting a fraction of these are implicated in AD. Here, we review the current evidence for six astrocytic transporter subfamilies involved in AD, as reported in both animal and human studies. This review confirms that astrocytes are indeed a viable target, highlights the complexities of studying astrocytes and provides future directives to exploit the potential of astrocytes in tackling AD.

A Tale of Two Diseases: Exploring Mechanisms Linking Diabetes Mellitus with Alzheimer’s Disease

2021 ◽  
pp. 1-17
Author(s):  
Jessica Lynn ◽  
Mingi Park ◽  
Christiana Ogunwale ◽  
George K. Acquaah-Mensah
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Mammalian Target Of Rapamycin ◽  
Insulin Receptors ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Main Component ◽  
The Impact

Dementias, including the type associated with Alzheimer’s disease (AD), are on the rise worldwide. Similarly, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases globally. Although mechanisms and treatments are well-established for T2DM, there remains much to be discovered. Recent research efforts have further investigated factors involved in the etiology of AD. Previously perceived to be unrelated diseases, commonalities between T2DM and AD have more recently been observed. As a result, AD has been labeled as “type 3 diabetes”. In this review, we detail the shared processes that contribute to these two diseases. Insulin resistance, the main component of the pathogenesis of T2DM, is also present in AD, causing impaired brain glucose metabolism, neurodegeneration, and cognitive impairment. Dysregulation of insulin receptors and components of the insulin signaling pathway, including protein kinase B, glycogen synthase kinase 3β, and mammalian target of rapamycin are reported in both diseases. T2DM and AD also show evidence of inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, and amyloid deposition. The impact that changes in neurovascular structure and genetics have on the development of these conditions is also being examined. With the discovery of factors contributing to AD, innovative treatment approaches are being explored. Investigators are evaluating the efficacy of various T2DM medications for possible use in AD, including but not limited to glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor-gamma agonists. Furthermore, there are 136 active trials involving 121 therapeutic agents targeting novel AD biomarkers. With these efforts, we are one step closer to alleviating the ravaging impact of AD on our communities.

scholarly journals Identification of Retinal Biomarkers in Alzheimer’s Disease Using Optical Coherence Tomography: Recent Insights, Challenges, and Opportunities

2019 ◽  
Vol 8 (7) ◽  
pp. 996 ◽  
Author(s):  
Delia Cabrera DeBuc ◽  
Magdalena Gaca-Wysocka ◽  
Andrzej Grzybowski ◽  
Piotr Kanclerz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Optical Coherence Tomography ◽  
Retinal Blood Flow ◽  
Optical Coherence ◽  
Ocular Diseases ◽  
Challenges And Opportunities ◽  
Retinal Structure ◽  
And Function ◽  
The Impact

This review will highlight recent insights into measuring retinal structure in Alzheimer’s disease (AD). A growing body of evidence indicates that disturbances in retinal blood flow and structure are related to cognitive function, which can severely impair vision. Optical coherence tomography (OCT) is an optical imaging technology that may allow researchers and physicians to gain deeper insights into retinal morphology and clarify the impact of AD on retinal health and function. Direct and noninvasive measurement of retinal morphology using OCT has provided useful diagnostic and therapeutic indications in several central nervous system (CNS) diseases, including AD, multiple sclerosis, and Parkinson disease. Despite several limitations, morphology assessment in the retinal layers is a significant advancement in the understanding of ocular diseases. Nevertheless, additional studies are required to validate the use of OCT in AD and its complications in the eye.

Acute Exercise and Cognitive Function in Alzheimer’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Ines Ben Ayed ◽  
Naomie Castor-Guyonvarch ◽  
Souad Amimour ◽  
Salma Naija ◽  
Chirine Aouichaoui ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Functions ◽  
Digit Span ◽  
Moderate Intensity ◽  
Current Evidence ◽  
Control Group ◽  
Maximal Heart Rate ◽  
Tower Of Hanoi ◽  
The Impact

Background: Many studies have shown the impact of acute aerobic exercises (AAE) on cognition in healthy adults or at a pre-dementia stage. Few studies, however, have explored the positive effects of AAE in moderate Alzheimer’s disease (ADM) patients. Objective: Evaluating the effect of AAE on cognitive functions in ADM patients. Methods: Overall, 79 (age: 69.62±0.99) ADM patients were recruited. Participants were divided into three groups according to the task: aerobic exercises done alone or combined with cognitive games presented on a screen, and a control group who performed a reading task. The aerobic exercise protocol consisted of a 20-min cycling exercise of moderate intensity, corresponding to 60%of the individual target maximal heart rate recorded in a 6-minute walking test. The participants’ cognition was monitored before and after the intervention using the Tower of Hanoi, Digit Span, and Stroop tasks. Results: After the exercise, the participants’ attention in both the physical and combined groups improved for the Stroop, the forward and backward Digit Span tasks, as well as the time taken to solve the Tower of Hanoi, although no significant differences were found in the number of moves taken in the latter. By contrast, the control group did not show any significant improvement for most of the cognitive tasks after the reading session. Conclusion: Current evidence suggests that AAE may help to improve cognitive functions in ADM patients. This improvement is enhanced when the exercise is combined with cognitive games. Safe and progressive types of exercises should be promoted among ADM patients.

scholarly journals The Impact of Meditation on the Cognitive Functions of Patients with Alzheimer’s Disease

2021 ◽  
Author(s):  
Maria Clara Lopes Rezende ◽  
Mariana Vanon Moreira ◽  
Bárbara Gomes Muffato ◽  
Yves Henrique Faria Dias ◽  
Ana Luíza Badini Tubenchlak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Function ◽  
Brain Network ◽  
Brain Structure And Function ◽  
Improve Sleep Quality ◽  
And Function ◽  
The Impact ◽  
The Brain ◽  
Positive Effect

Introduction: Alzheimer’s disease (AD) is the most common form of dementia, which has no cure and, also, effective therapies to prevent or slow the progression of AD remain elusive. Thus, it is necessary to find another way to treat this disease Objective: Investigate the impact of meditation on the cognitive function of patients with AD. Methods: In April 2021, a systematic review was carried out on MEDLINE using the descriptors: “Meditation” and “Alzheimer Disease” and their variations. Studies published in the last 10 years and in English were included. Results: Of the 40 articles found, four are part of this review. It was showed that meditation generates improvements in memory as it increases cerebral blood flow, stabilizes synapses and elevates important neurotransmitters. Aligned, it can improve sleep quality and retrospective memory function. Furthermore, daily practices help in neuropsychological conditions and generate beneficial changes in brain structure and function. Finally, it provokes changes in the brain network, such as the increased power of the theta band, involved in memory processes. Conclusion: The results imply a positive effect of meditation on patients with AD. However, further research is needed to confirm the validity of the results.

scholarly journals Biomarkers to Evaluate Androgen Deprivation Therapy for Prostate Cancer and Risk of Alzheimer’s Disease and Neurodegeneration: Old Drugs, New Concerns

2021 ◽  
Vol 11 ◽  
Author(s):  
Vérane Achard ◽  
Kelly Ceyzériat ◽  
Benjamin B. Tournier ◽  
Giovanni B. Frisoni ◽  
Valentina Garibotto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cancer Patients ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Cortical Activation ◽  
Current Evidence ◽  
The Impact

Androgen deprivation therapy (ADT) is a standard treatment for prostate cancer patients, routinely used in the palliative or in the curative setting in association with radiotherapy. Among the systemic long-term side effects of ADT, growing data suggest a potentially increased risk of dementia/Alzheimer’s disease in prostate cancer patients treated with hormonal manipulation. While pre-clinical data suggest that androgen ablation may have neurotoxic effects due to Aβ accumulation and increased tau phosphorylation in small animal brains, clinical studies have measured the impact of ADT on long-term cognitive function, with conflicting results, and studies on biological changes after ADT are still lacking. The aim of this review is to report on the current evidence on the association between the ADT use and the risk of cognitive impairment in prostate cancer patients. We will focus on the contribution of Alzheimer’s disease biomarkers, namely through imaging, to investigate potential ADT-induced brain modifications. The evidence from these preliminary studies shows brain changes in gray matter volume, cortical activation and metabolism associated with ADT, however with a large variability in biomarker selection, ADT duration and cognitive outcome. Importantly, no study investigated yet biomarkers of Alzheimer’s disease pathology, namely amyloid and tau. These preliminary data emphasize the need for larger targeted investigations.

PINK1 Activation Attenuates Impaired Neuronal-Like Differentiation and Synaptogenesis and Mitochondrial Dysfunction in Alzheimer’s Disease Trans-Mitochondrial Cybrid Cells

2021 ◽  
pp. 1-13
Author(s):  
Fang Du ◽  
Qing Yu ◽  
Shirley ShiDu Yan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Energy Homeostasis ◽  
Early Stage ◽  
Mitochondrial Morphology ◽  
Mitochondrial Functions ◽  
Lentivirus Transduction ◽  
And Function ◽  
Human Brains

Background: Mitochondrial dysfunction, bioenergetic deficit, and extensive oxidative stress underlie neuronal perturbation during the early stage of Alzheimer’s disease (AD). Previously, we demonstrated that decreased PTEN-induced putative kinase 1 (PINK1) expression is associated with AD pathology in AD-affected human brains and AD mice. Objective: In the present study, we highlight the essential role of PINK1 in AD-relevant mitochondrial perturbation and neuronal malfunction. Methods: Using trans-mitochondrial “cybrid” (cytoplasmic hybrid) neuronal cells, whose mitochondria are transferred from platelets of patients with sporadic AD, we observed the effect of PINK1 in neuronal-like differentiation and synaptogenesis and mitochondrial functions. Results: In AD cybrid cells, the downregulation of PINK1 is correlated to the alterations in mitochondrial morphology and function and deficit in neuronal-like differentiation. Restoring/increasing PINK1 by lentivirus transduction of PINK1 robustly attenuate mitochondrial defects and rescue neurite-like outgrowth. Importantly, defective PINK1 kinase activity fails to reverse these detrimental effects. Mechanistically, AD cybrid cells reveal a significant decrease in PINK1-dependent phosphorylated mitofusin (Mfn) 2, a key mitochondrial membrane protein that participates in mitochondrial fusion, and an insufficient autophagic activity for clearance of dysfunctional mitochondria. Overexpression of PINK1, but not mutant PINK1 elevates phosphorylation of Mfn2 and autophagy signaling LC3-II. Accordingly, PINK1-overexpressed AD cybrids exhibit increases in mitochondrial length and density and suppressed reactive oxygen species. These results imply that activation of PINK1 protects against AD-affected mitochondrial dysfunction and impairment in neuronal maturation and differentiation. Conclusion: PINK1-mediated mitophagy is important for maintaining mitochondrial health by clearance of dysfunctional mitochondria and therefore, improves energy homeostasis in AD.

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