It's Been a Long Time Coming: The Ups and Downs of the First New Agent for Alzheimer’s Disease Since 2003

2022 ◽  
Vol 37 (1) ◽  
pp. 4-5
Author(s):  
Lawrence J. Cohen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Long Time

scholarly journals ROLE OF PATHOGENIC PROTEINS AND CHRONIC INFLAMMATION IN THE OCCURRENCE OF ALZHEIMER'S DISEASE

2020 ◽  
Vol 8 (4) ◽  
pp. 475-490
Author(s):  
A.P. Denysenko ◽  
O.O. Haikova ◽  
R.A. Moskalenko
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Economic Significance ◽  
Leading Role ◽  
Vascular Insufficiency ◽  
Scientific Papers ◽  
Long Time ◽  
Β Amyloid ◽  
Key Terms

Alzheimer's disease is the most common form of dementia affecting up to 70% of all patients with dementia. Currently, the relevance of this neurodegenerative disease has increased due to its prevalence and lack of etiological and effective treatment. The consequence of this is an increase in the number of studies and scientific works aimed at studying this disease. The aim of the study was to analyze and systematize data on the prevalence, socioeconomic significance, theories of origin, as well as the role of pathogenic proteins in the development of Alzheimer's disease. The authors searched for information in electronic databases such as PubMed and Google Scholar, with scientific papers and articles from the last 25 years on such key terms as Alzheimer's disease, β-amyloid, tau-peptide, metals, inflammation, S100 proteins. There are more than 56 million people with Alzheimer's disease in the world and the risk increases with age. Among the causes of death, Alzheimer's disease ranks sixth, and the costs of care about person with this diagnosis are three times higher than for other diseases in the same age group. That is why this issue has significant socio-economic significance. Many hypotheses have emerged in recent decades. For a long time, the theory of β-amyloid aggregation and the theory of tau protein were considered main, but later the priorities began to change. It has been found that the presence of pathogenic microorganisms can pose a risk for Alzheimer's disease. Also, some studies indicate the role of acetylcholine in the development of the disease, however, clinical trials have not confirmed this. There is a violation of metal homeostasis, which contributes to cognitive deficits and the development of neurodegeneration. Microglia, astrocytes and neurons are involved in the inflammatory process in Alzheimer's disease. There is a vicious circle when Aβ causes vascular insufficiency, which in turn leads to an increase in Aβ accumulation. Also there is evidence of a direct relationship between oxidative stress and neuronal dysfunction. Undoubtedly, pathogenic proteins, including Aβ-peptide, tau-peptide and proteins of the S100 family, play a leading role in the development of Alzheimer's disease. Despite numerous studies, the causal or consequential role of various pathological factors and changes in Alzheimer's disease is still ambiguous and inconsistent. All this gives grounds for further scientific research in this direction.

scholarly journals Patients with dementia and depression-complexity

2018 ◽  
Vol 2 (3) ◽  
pp. 01-03
Author(s):  
Samuel Langhorne
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
The Elderly ◽  
Long Time

For a long time researchers and clinicians have been trying to clarify the possible existing relationships between Alzheimer’s disease and the depression in the elderly. This article tries to take stock of these complex links. It seems that often depression is clinically confused with apathy.

scholarly journals Beta Amyloid, Tau Protein, and Neuroinflammation: An Attempt to Integrate Different Hypotheses of Alzheimer’s Disease Pathogenesis

2021 ◽  
Vol 55 (5) ◽  
pp. 670-682
Author(s):  
D. G. Garbuz ◽  
O. G. Zatsepina ◽  
M. B. Evgen’ev
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Responses ◽  
Clinical Results ◽  
Current Treatment ◽  
Amyloid Peptide ◽  
Treatment Regimens ◽  
Leading Role ◽  
Long Time ◽  
Β Amyloid Peptide

Abstract Alzheimer’s disease (AD) is a neurodegenerative disease that inevitably results in dementia and death. Currently, there are no pathogenetically grounded methods for the prevention and treatment of AD, and all current treatment regimens are symptomatic and unable to significantly delay the development of dementia. The accumulation of β-amyloid peptide (Aβ), which is a spontaneous, aggregation-prone, and neurotoxic product of the processing of signaling protein APP (Amyloid Precursor Protein), in brain tissues, primarily in the hippocampus and the frontal cortex, was for a long time considered the main cause of neurodegenerative changes in AD. However, attempts to treat AD based on decreasing Aβ production and aggregation did not bring significant clinical results. More and more arguments are arising in favor of the fact that the overproduction of Aβ in most cases of AD is not the initial cause, but a concomitant event of pathological processes in the course of the development of sporadic AD. The concept of neuroinflammation has come to the fore, suggesting that inflammatory responses play the leading role in the initiation and development of AD, both in brain tissue and in the periphery. The hypothesis about the key role of neuroinflammation in the pathogenesis of AD opens up new opportunities in the search for ways to treat and prevent this socially significant disease.

scholarly journals Frontotemporal dementia to Alzheimer's disease

2007 ◽  
Vol 9 (2) ◽  
pp. 153-160
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Dementia ◽  
Behavioral Changes ◽  
Neural Damage ◽  
Personality Changes ◽  
The Social ◽  
Long Time ◽  
And Behavior ◽  
The Relationship

Behavioral manifestations may dominate the clinical picture of the frontal variant of frontotemporal dementia (fv-FTD) for a long time before the appearance of true cognitive deficits. On the other hand, a deficit in the episodic memory domain represents the main manifestation of Alzheimer's disease (AD). Many behavioral disorders have been described in the clinical course of both FTD and AD; however, apathy and personality changes characterize frontal dementias, while depression dominates in AD, at least in the earlier stages. Depending on the distribution of neural damage, different patterns of noncognitive manifestations may be expected in different subtypes of FTD. Recent research on the social cognition deficit in FTD has offered new insights into the relationship between cognition and behavior, suggesting that some aspects of the behavioral changes in dementia may be generated by impairment in this domain.

scholarly journals Devotion and Commitment in A Contradictory Conditionsas Seen in The Notebook by Nicholas Spark

2020 ◽  
Vol 3 (2) ◽  
pp. 17-31
Author(s):  
Helmita Helmita ◽  
Elsa Mayora Putri
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Qualitative Method ◽  
Descriptive Analysis ◽  
The Novel ◽  
Analysis Method ◽  
Personality Psychology ◽  
Long Time ◽  
First Time ◽  
The Relationship

The problem in this thesis is Devotion and commitment in a contradictory conditions in the relationship between Noah and Allie who have differences in social status. Until their relationship was opposed by Allie's mother, even so Allie remained devotion to choose Noahh. Devotion and commitment to the contradictory conditions between Noah and Allie also occur when they are old. Noah remained loyal to Allie when she suffered from Alzheimer's disease. The object of this study was The Notebook novel by Nicholas Sparks. This research uses Sigmund Freud's theory of personality psychology. The results of this study are the figures Noah and Alli have personality aspects that refer to Sigmund Freud's theory of id, ego, superego. The writer uses descriptive analysis method and qualitative method. The author carries out a systematic procedure with an understanding of the novel, figures Noah and Allie, and also structural theory. This research aims : (1) to analyze the importance of loyalty and commitment in contradictory conditions. (2) to describe the loyalty and commitment contained in the Novel The notebook. (3) to explain the loyalty and commitment shown by Noah and Allie after marriage. Based on the results of this analysis it can be concluded that the problem faced by the main character is his deep love and loyalty to his wife, Noah did everything for Allie, including writing to him for two years even though his letter was never responded by Allie. But when they met for the first time after being separated for quite a long time their love for each other was still there. Until they married and aged together and Allie contracted Alzheimer's disease, but Noah remained faithful with her.

scholarly journals AβInternalization by Neurons and Glia

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Amany Mohamed ◽  
Elena Posse de Chaves
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Strong Evidence ◽  
Molecular Mechanisms ◽  
Neuronal Dysfunction ◽  
Intracellular Accumulation ◽  
Extracellular Milieu ◽  
Long Time ◽  
The Brain

In the brain, the amyloidβpeptide (Aβ) exists extracellularly and inside neurons. The intracellular accumulation of Aβin Alzheimer's disease brain has been questioned for a long time. However, there is now sufficient strong evidence indicating that accumulation of Aβinside neurons plays an important role in the pathogenesis of Alzheimer's disease. Intraneuronal Aβoriginates from intracellular cleavage of APP and from Aβinternalization from the extracellular milieu. We discuss here the different molecular mechanisms that are responsible for Aβinternalization in neurons and the links between Aβinternalization and neuronal dysfunction and death. A brief description of Aβuptake by glia is also presented.

Advanced protein drugs and formulations

2021 ◽  
Vol 22 ◽  
Author(s):  
Luciano Benedini
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Celiac Disease ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
The Body ◽  
Protein Drugs ◽  
Long Time ◽  
Type Of Behavior

: For a long time, proteins were a subset of molecules rarely applied as therapeutically active molecules. Some of the first applications of proteins as drugs have been insulin and vaccines for supply a physiological deficiency and the prevention of diseases, respectively. Nowadays, proteins have increased their range of application, not only as drugs but also as drug delivery systems to be administered by different routes. Due to their nature, proteins show different behavior while the conditions of the environment are modified. For this reason, it has been necessary to study their behavior for predicting the correct manufacturing, storing, or combination with other possible molecules in a formulation or into the body. The application of techniques for predicting the behavior of proteins in different environments has led to associate this type of behavior into the body with the occurrence of diseases such as celiac disease or Alzheimer's disease. Thus, this work shows an overview of the main types of proteins applied as active therapeutically molecules, proteins-based drug delivery systems, and techniques for predicting their stability into the storing container and the body.

scholarly journals Exploring the Applications of Phosphodiesterase Inhibitors Beyond Erectile Dysfunction

2020 ◽  
pp. 18-29
Author(s):  
Ihab Mansoor ◽  
Mark Mikhail ◽  
Abigail Wiss ◽  
Diana Huynh ◽  
Monica Oakes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Erectile Dysfunction ◽  
Phosphodiesterase Inhibitors ◽  
Therapeutic Agents ◽  
Delivery Methods ◽  
Therapeutic Applications ◽  
Pde Inhibitors ◽  
Long Time ◽  
Camp And Cgmp

Phosphodiesterases (PDEs) represent a class of enzymes that act mainly on cAMP and cGMP. The value of these enzymes has been known for long time. Molecules that target PDEs have been used in various therapeutic applications. This review aims to explore the potential uses of PDE inhibitors (PDEIs) as therapeutic agents to treat conditions that extend beyond erectile dysfunction (ED), as well as highlight novel delivery methods for PDEIs. Keywords: Phosphodiesterase inhibitors; Alzheimer’s disease; Cognition; Psoriasis; Sildenafil

scholarly journals Study on the cause and pathogenesis of Alzheimer's disease

2019 ◽  
Author(s):  
zuodong sun
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Cell Activation ◽  
Amyloid Plaques ◽  
Brain Cell ◽  
Research Field ◽  
Brain Cells ◽  
Sporadic Alzheimer’S Disease ◽  
Long Time

An enlightening viewpoint based on the theory of brain cell activation is to explore the pathogenesis and mechanism of sporadic Alzheimer's disease (AD) at molecular level by applying the principles of cell physics and biology. Its purpose is to coordinate and unify the existing theories of AD etiology and to solve the problems that have puzzled the research field of neurodegenerative diseases for a long time. Basic Contents: Excessive cations are transferred from extracellular to intracellular, and compete with potassium ions on the inner surface of the cell membrane. As a result, the action potential produced can not activate calcium channels normally, leading to abnormal apoptosis of brain cells. Amyloid plaques are the remains of abnormal apoptotic brain cells. Amyloid plaques are aggregated by van der Waals force and electrostatic attraction between amyloid plaques. The interstitium is amyloid protein. Brain cells consist of neurons, microglia and astrocytes in turn. Most of the spotted nuclei in the remains are cations. Applicable but not limited to neurodegenerative diseases such as Alzheimer's disease, physical means should be preferred to solve such diseases.

scholarly journals microRNAs as Early Biomarkers of Alzheimer’s Disease: A Synaptic Perspective

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 113
Author(s):  
Dolores Siedlecki-Wullich ◽  
Alfredo J. Miñano-Molina ◽  
José Rodríguez-Álvarez
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Time Window ◽  
Cost Effective ◽  
Synaptic Function ◽  
Therapeutic Interventions ◽  
Synaptic Homeostasis ◽  
Diagnosis And Prognosis ◽  
Individual Mirnas ◽  
Long Time

Pathogenic processes underlying Alzheimer’s disease (AD) affect synaptic function from initial asymptomatic stages, long time before the onset of cognitive decline and neurodegeneration. Therefore, reliable biomarkers enabling early AD diagnosis and prognosis are needed to maximize the time window for therapeutic interventions. MicroRNAs (miRNAs) have recently emerged as promising cost-effective and non-invasive biomarkers for AD, since they can be readily detected in different biofluids, including cerebrospinal fluid (CSF) and blood. Moreover, a growing body of evidence indicates that miRNAs regulate synaptic homeostasis and plasticity processes, suggesting that they may be involved in early synaptic dysfunction during AD. Here, we review the current literature supporting a role of miRNAs during early synaptic deficits in AD, including recent studies evaluating their potential as AD biomarkers. Besides targeting genes related to Aβ and tau metabolism, several miRNAs also regulate synaptic-related proteins and transcription factors implicated in early synaptic deficits during AD. Furthermore, individual miRNAs and molecular signatures have been found to distinguish between prodromal AD and healthy controls. Overall, these studies highlight the relevance of considering synaptic-related miRNAs as potential biomarkers of early AD stages. However, further validation studies in large cohorts, including longitudinal studies, as well as implementation of standardized protocols, are needed to establish miRNA-based biomarkers as reliable diagnostic and prognostic tools.

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