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Advanced Diagnostic and Treatment Methods in Alzheimer's Disease

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 9044

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Special Issue Editor

Dr. Athanasios Alexiou

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Guest Editor

Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia and AFNP Med Austria, 1030 Wien, Austria
Interests: computational biomedicine; biomarkers; neuroscience; infectious diseases; cancer

Special Issue Information

Dear Colleagues,

Alzheimer's disease (AD) is a form of dementia and the most common progressive neurodegenerative disease. Alzheimer's disease affects approximately 50 million individuals worldwide according to estimates. It is predicted that this number will rise to 150 million by 2050 unless new preventative medicines or very effective diagnostic tools are developed.

In AD, oxidative stress resulting from mitochondrial dysfunction is posited to result from pathological progress yet to be determined. Additionally, targeting amyloid-beta (Aβ) aggregation is one of the most widely used strategies to manage AD, and efforts are being made globally to develop peptide-based compounds for an efficient early diagnosis and treatment. Peptides are a special pharmacological agent that falls between small molecules and proteins. This vast pool of bioactive compounds holds considerable potential for treating hitherto difficult-to-treat oncological, metabolic, viral, and neurological diseases. The latest studies have led to the development of drugs that target Aβ (β and γ-Secretase inhibitors) to reduce the amount of Aβ formed, even though these inhibitors might be associated with harmful side effects, low efficacy, and inability to cross the blood–brain barrier. Furthermore, phytocompounds, especially alkaloids, were known for their anti-AD treatment value applications, based on in vitro and in vivo studies, along with anti-aggregating compounds, metal chelators, and anti-oxidative agents, and anti-inflammatory drugs.

To provide a dynamic insight into the AD challenge, this Special Issue aims to reveal anti-AD treatments and additional computational tools for early diagnosis and prediction of the disease and other comorbidities.

We invite authors to submit original research and review articles that focus on, but are not limited to, the following potential topics:

Alzheimer's disease;
Amyloid-beta;
Antidiabetic drugs in neurodegeneration;
Cancer and Alzheimer’s disease;
Computational biomedicine;
Cubosomes;
Drug targets;
In silico;
Lipids;
Machine learning approach;
Mitochondria;
Neurodegeneration;
Neuroinflammation;
Oxidative stress;
Phytocompounds in Alzheimer’s disease;
Β secretase and γ-secretase inhibitors.

Dr. Athanasios Alexiou
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Alzheimer's disease
amyloid-beta
antidiabetic drugs in neurodegeneration
cancer and Alzheimer's disease
computational biomedicine
cubosomes
drug targets
insilico
lipids
machine-learning approach
mitochondria
neurodegeneration
neuroinflammation
oxidative stress
phytocompounds in Alzheimer's disease
β secretase and γ-secretase inhibitors

Published Papers (4 papers)

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Research

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19 pages, 3612 KiB

Open AccessArticle

Neuroprotective Potential of Raloxifene via G-Protein-Coupled Estrogen Receptors in Aβ-Oligomer-Induced Neuronal Injury

by Tetsuhito Nohara, Mayumi Tsuji, Tatsunori Oguchi, Yutaro Momma, Hideaki Ohashi, Miki Nagata, Naohito Ito, Ken Yamamoto, Hidetomo Murakami and Yuji Kiuchi

Biomedicines 2023, 11(8), 2135; https://doi.org/10.3390/biomedicines11082135 - 28 Jul 2023

Cited by 2 | Viewed by 1280

Abstract

Amyloid-β (Aβ) is one of the causes of Alzheimer’s disease (AD), damaging nerve membranes and inducing neurotoxicity. AD is more prevalent in female patients than in male patients, and women are more susceptible to developing AD due to the decline in estrogen levels around menopause. Raloxifene, a selective estrogen receptor modulator, exhibits protective effects by activating the transmembrane G-protein-coupled estrogen receptor (GPER). Additionally, raloxifene prevents mild cognitive impairment and restores cognition. However, the influence of raloxifene via GPER on highly toxic Aβ-oligomers (Aβo)-induced neurotoxicity remains uncertain. In this study, we investigated the GPER-mediated neuroprotective effects of raloxifene against the neurotoxicity caused by Aβo-induced cytotoxicity. The impact of raloxifene on Aβo-induced cell damage was evaluated using measures such as cell viability, production of reactive oxygen species (ROS) and mitochondrial ROS, peroxidation of cell-membrane phospholipids, and changes in intracellular calcium ion concentration ([Ca²⁺]_i) levels. Raloxifene hindered Aβo-induced oxidative stress and reduced excessive [Ca²⁺]_i, resulting in improved cell viability. Furthermore, these effects of raloxifene were inhibited with pretreatment with a GPER antagonist. Our findings suggest that raloxifene safeguards against Aβo-induced neurotoxicity by modifying oxidative parameters and maintaining [Ca²⁺]_i homeostasis. Raloxifene may prove effective in preventing and inhibiting the progression of AD. Full article

(This article belongs to the Special Issue Advanced Diagnostic and Treatment Methods in Alzheimer's Disease)

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11 pages, 2486 KiB

Open AccessArticle

Discordant Amyloid Status Diagnosis in Alzheimer’s Disease

by Lorena García-Vallés, Carmen Peña-Bautista, Lourdes Álvarez-Sánchez, Inés Ferrer-Cairols, Miguel Baquero and Consuelo Cháfer-Pericás

Biomedicines 2022, 10(11), 2880; https://doi.org/10.3390/biomedicines10112880 - 10 Nov 2022

Viewed by 1136

Abstract

Introduction: Early and accurate Alzheimer’s disease (AD) diagnosis has evolved in recent years by the use of specific methods for detecting its histopathological features in concrete cases. Currently, biomarkers in cerebrospinal fluid (CSF) and imaging techniques (amyloid PET) are the most used specific methods. However, some results between both methods are discrepant. Therefore, an evaluation of these discrepant cases is required. Objective: The aim of this work is to analyze the characteristics of cases showing discrepancies between methods for detecting amyloid pathology. Methodology: Patients from the Neurology Department of La Fe Hospital (n = 82) were diagnosed using both methods (CSF biomarkers and amyloid-PET). Statistical analyses were performed using logistic regression, and sex and age were included as covariables. Additionally, results of standard neuropsychological evaluations were taken into account in our analyses. Results: The comparison between CSF biomarker (Aβ42) and amyloid PET results showed that around 18% of cases were discrepant—mainly CFS-negative and PET-positive cases had CSF levels close to the cut-off point. In addition, a correlation between the episodic memory test and CSF biomarkers levels was observed. However, the same results were not obtained for other neuropsychological domains. In general, CSF- and PET-discrepant cases showed altered episodic memory in around 66% of cases, while 33% showed normal performance. Conclusions: In common clinical practice at tertiary memory centers, result discrepancies between tests of amyloid status are far more common than expected. However, episodic memory tests remain an important support method for AD diagnosis, especially in cases with discrepant results between amyloid PET and CSF biomarkers. Full article

(This article belongs to the Special Issue Advanced Diagnostic and Treatment Methods in Alzheimer's Disease)

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Review

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31 pages, 1454 KiB

Open AccessReview

The Future of Precision Medicine in the Cure of Alzheimer’s Disease

by Azher Arafah, Saima Khatoon, Iyman Rasool, Andleeb Khan, Mashoque Ahmad Rather, Khaled Abdullah Abujabal, Yazid Abdullilah Hassan Faqih, Hina Rashid, Shahzada Mudasir Rashid, Sheikh Bilal Ahmad, Athanasios Alexiou and Muneeb U. Rehman

Biomedicines 2023, 11(2), 335; https://doi.org/10.3390/biomedicines11020335 - 25 Jan 2023

Cited by 10 | Viewed by 3516

Abstract

This decade has seen the beginning of ground-breaking conceptual shifts in the research of Alzheimer’s disease (AD), which acknowledges risk elements and the evolving wide spectrum of complicated underlying pathophysiology among the range of diverse neurodegenerative diseases. Significant improvements in diagnosis, treatments, and mitigation of AD are likely to result from the development and application of a comprehensive approach to precision medicine (PM), as is the case with several other diseases. This strategy will probably be based on the achievements made in more sophisticated research areas, including cancer. PM will require the direct integration of neurology, neuroscience, and psychiatry into a paradigm of the healthcare field that turns away from the isolated method. PM is biomarker-guided treatment at a systems level that incorporates findings of the thorough pathophysiology of neurodegenerative disorders as well as methodological developments. Comprehensive examination and categorization of interrelated and convergent disease processes, an explanation of the genomic and epigenetic drivers, a description of the spatial and temporal paths of natural history, biological markers, and risk markers, as well as aspects about the regulation, and the ethical, governmental, and sociocultural repercussions of findings at a subclinical level all require clarification and realistic execution. Advances toward a comprehensive systems-based approach to PM may finally usher in a new era of scientific and technical achievement that will help to end the complications of AD. Full article

(This article belongs to the Special Issue Advanced Diagnostic and Treatment Methods in Alzheimer's Disease)

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14 pages, 1170 KiB

Open AccessReview

The “Cerebrospinal Fluid Sink Therapeutic Strategy” in Alzheimer’s Disease—From Theory to Design of Applied Systems

by Thomas Gabriel Schreiner, Manuel Menéndez-González and Bogdan Ovidiu Popescu

Biomedicines 2022, 10(7), 1509; https://doi.org/10.3390/biomedicines10071509 - 25 Jun 2022

Cited by 6 | Viewed by 1942

Abstract

Alzheimer’s disease (AD) is a global health problem, with incidence and prevalence considered to increase during the next decades. However, no currently available effective treatment exists despite numerous clinical trials in progress. Moreover, although many hypotheses are accepted regarding the pathophysiological mechanisms of AD onset and evolution, there are still many unknowns about the disorder. A relatively new approach, based on the amyloid-beta dynamics among different biological compartments, is currently intensely discussed, as it seems to offer a promising solution with significant therapeutic impact. Known as the “cerebrospinal-fluid-sink therapeutic strategy”, part of the “three-sink therapeutic strategy”, this theoretical model focuses on the dynamics of amyloid-beta among the three main liquid compartments of the human body, namely blood, cerebrospinal fluid, and the (brain) interstitial fluid. In this context, this article aims to describe in detail the abovementioned hypothesis, by reviewing in the first part the most relevant anatomical and physiological aspects of amyloid-beta dynamics. Subsequently, explored therapeutic strategies based on the clearance of amyloid-beta from the cerebrospinal fluid level are presented, additionally highlighting their limitations. Finally, the originality and novelty of this work rely on the research experience of the authors, who focus on implantable devices and their utility in AD treatment. Full article

(This article belongs to the Special Issue Advanced Diagnostic and Treatment Methods in Alzheimer's Disease)

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