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To assess the variations and diagnostic performance of serum biomarkers of neurodegenerative diseases. In this monocentric prospective study, neurofilament light (NFL), T-tau, p-tau181, p-tau217, Aβ40, and Aβ42 were measured in serum collected from orthopedic patients (control group, n=114) and patients in the neurology department (n=69) previously diagnosed with Alzheimer's disease (AD, n=52), parkinsonian syndromes (n=10), and other etiologies of neurodegeneration (non-AD, n=7). In the control group, serum NFL, T-tau, p-tau181, p-tau217, and Aβ40 significantly increased with age, independently of sex. NFL (p=0.0078), p-tau217 (p<0.001) were significantly increased with neurodegeneration when compared to controls, with only p-tau217 significant in the multivariate analysis (p<0.001). Multivariate regression analysis accounting for age highlighted a significant increase of p-tau217 (p<0.001) in the AD subgroup. NFL was significantly increased in the non-AD patients (p<0.001), and in the parkinsonian syndromes subgroup (p=0.016) when compared to negative controls. Serum p-tau181 and p-tau217 were significantly correlated with CSF p-tau181 (Spearman's coefficients of 0.43 and 0.48 respectively, n=40). Areas under the ROC curves for the identification of patients with neurodegenerative diseases were 0.62 (0.54–0.70) for NFL, 0.62 (0.54–0.71) for T-tau, 0.83 (0.76–0.89) for p-tau217, and 0.66 (0.58–0.74) for Aβ40. Serum biomarkers can help identify patients with neurodegenerative disease and may be a valuable tool for care and orientation. Phosphorylated tau p-tau217 is a promising blood biomarker for AD and NFL for other etiologies. [ABSTRACT FROM AUTHOR]

Copyright of Gériatrie et Psychologie Neuropsychiatrie du Vieillissement is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The onset and progression of a neurological disease can often be explained in terms of brain-network alteration. They can be formalized as the action of an operator representing the disease, the so-called /C-operator, acting on the network. The healing process can thus be seen as the inverse of the disease mechanism. However, perfect healing is often impossible to achieve. Here, we formalize the ideal healing in terms of perturbative variation of the possible partial healing. The modeling and analytical strategy is based on techniques from theoretical physics, with the language of matrix operators. In addition, using the language of category theory, we also formalize the progressive abstraction from the reality of diseased patients to the definition of a disease and the comparison between different diseases as a natural transformation between colimits. This theoretical presentation can provide a new, interdisciplinary perspective on neurological investigation and possibly foster new theoretical-experimental developments. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive and irreversible neurological condition that occurs with age and poses a significant global public health concern, is distinguished by the degeneration of neurons and synapses in various regions of the brain. While the exact processes behind the neurodegeneration in AD are not completely known, it is now acknowledged that inflammation may have a significant impact on the beginning and advancement of AD neurodegeneration. The severity of many neurological illnesses can be influenced by the equilibrium between pro-inflammatory and anti-inflammatory mediators. The IL-1 family of cytokines is linked to innate immune responses, which are present in both acute inflammation and chronic inflammatory diseases. Research on the role of the IL-1 family in chronic neurological disease has been concentrated on AD. In this context, there is indirect evidence suggesting its involvement in the development of the disease. This review aims to provide a summary of the contribution of every IL-1 family member in AD pathogenesis, current immunotherapies in AD disease, and present treatment possibilities for either targeting or boosting these cytokines. [ABSTRACT FROM AUTHOR]

The amyloid-cascade-hypothesis of the pathogenesis of Alzheimer's disease (AD) was introduced 32 years ago, in 1992. From early on, this clear and straight forward hypothesis received a lot of attention, but also a lot of substantial criticism. Foremost, there have always been massive doubts that a complex age-associated disorder of the most intricate organ of the human body, the brain, can be explained by a linear, one-dimensional cause-and-effect model. The amyloid-cascade defines the generation, aggregation, and deposition of the amyloid beta peptide as the central pathogenic mechanism in AD, as the ultimate trigger of the disease, and, consequently, as the key pharmacological target. Certainly, the original 1992 version of this hypothesis has been refined by various means, and the 'formulating fathers' followed up with a few reappraisals and partly very open reflections in 2002, 2006, 2009, and 2016. However, up until today, for the supporters of this hypothesis, the central and initial steps of the cascade are believed to be driven by amyloid beta--even if now displayed somewhat more elaborate. In light of the recently published clinical results achieved with anti-amyloid antibodies, the controversy in the field about (1) the clinical meaningfulness of this approach, (2) the significance of clearance of the amyloid beta peptide, and last but not least (3) the relevance of the amyloid-cascade-hypothesis is gaining momentum. This review addresses the interesting manifestation of the amyloid-cascade-hypothesis as well as its ups and downs over the decades. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most prevalent form of neurodegeneration. Despite the well-established link between tau aggregation and clinical progression, the major pathways driven by this protein to intrinsically damage neurons are incompletely understood. To model AD-relevant neurodegeneration driven by tau, we overexpressed non-mutated human tau in primary mouse neurons and observed substantial axonal degeneration and cell death, a process accompanied by activated caspase 3. Mechanistically, we detected deformation of the nuclear envelope and increased DNA damage response in tau-expressing neurons. Gene profiling analysis further revealed significant alterations in the mitogen-activated protein kinase (MAPK) pathway; moreover, inhibitors of dual leucine zipper kinase (DLK) and c-Jun N-terminal kinase (JNK) were effective in alleviating wild-type human tau-induced neurodegeneration. In contrast, mutant P301L human tau was less toxic to neurons, despite causing comparable DNA damage. Axonal DLK activation induced by wild-type tau potentiated the impact of DNA damage response, resulting in overt neurotoxicity. In summary, we have established a cellular tauopathy model highly relevant to AD and identified a functional synergy between the DLK-MAPK axis and DNA damage response in the neuronal degenerative process.

The tau protein is a key contributor to multiple neurodegenerative diseases. The pathology of tau is thought to be related to tau's propensity to form self-templating fibrillar structures that allow tau fibers to propagate in the brain by prion-like mechanisms. Unresolved issues with respect to tau pathology are how the normal function of tau and its misregulation contribute to disease, how cofactors and cellular organelles influence the initiation and propagation of tau fibers, and determining the mechanism of tau toxicity. Herein, we review the connection between tau and degenerative diseases, the basis for tau fibrilization, and how that process interacts with cellular molecules and organelles. One emerging theme is that tau interacts with RNA and RNA-binding proteins, normally and in pathologic aggregates, which may provide insight into alterations in RNA regulation observed in disease. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Inpp5d is genetically associated with Alzheimer's disease risk. Loss of Inpp5d alters amyloid pathology in models of amyloidosis. Inpp5d is expressed predominantly in microglia but its function in brain is poorly understood. METHODS: We performed single‐cell RNA sequencing to study the effect of Inpp5d loss on wild‐type mouse brain transcriptomes. RESULTS: Loss of Inpp5d has sex‐specific effects on the brain transcriptome. Affected genes are enriched for multiple neurodegeneration terms. Network analyses reveal a gene co‐expression module centered around Inpp5d in female mice. Inpp5d loss alters Pleotrophin (PTN), Prosaposin (PSAP), and Vascular Endothelial Growth Factor A (VEGFA) signaling probability between cell types. DISCUSSION: Our data suggest that the normal function of Inpp5d is entangled with mechanisms involved in neurodegeneration. We report the effect of Inpp5d loss without pathology and show that this has dramatic effects on gene expression. Our study provides a critical reference for researchers of neurodegeneration, allowing separation of disease‐specific changes mediated by Inpp5d in disease from baseline effects of Inpp5d loss. Highlights: Loss of Inpp5d has different effects in male and female mice.Genes dysregulated by Inpp5d loss relate to neurodegeneration.Total loss of Inpp5d in female mice collapses a conserved gene co‐expression module.Loss of microglial Inpp5d affects the transcriptome of other cell types. [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Situated within the broad spectrum of neurodegenerative disorders, Alzheimer's disease (AD) is known for its complexity, heterogeneity, multiple genetic mutations, epigenetic and biochemical modifications, and irreversible progression from early stages characterized by deficits in the ability to encode and store new information to subsequent progressive cognitive, functional, and behavioral decline. The conducted study aimed to compile conclusive statistics, identify genetic factors, and correlate them with environmental ones, thus highlighting the importance of developing evaluation programs and early introduction of medication to decelerate the progression of neurodegenerative processes. The analytical, observational, retrospective study was conducted on an extended cohort of 2277 patients admitted with chronic neurological diseases to the Neurology Department of "Dr. Iacob Czihac" Clinical Military Emergency Hospital Iași from January 1, 2022, to December 31, 2023. Among these, 219 patients were diagnosed with AD at various stages. Forty-three cases exhibiting genetic predisposition (19.63%) were selected and thoroughly analyzed based on medical records. The study emphasizes the significant position of AD among chronic neurological diseases. Although the majority do not present hereditary antecedents (80.36%), predisposing conditions, environmental factors, stress, and the region of residence play fundamental roles in the disease's determinism. It is observed that individuals in the 60-70 age category (71.23%) from urban areas (63.01%), especially females (63.47%), have a higher probability of developing AD. Maternally transmitted AD prevalence was 58.13%, while paternally inherited AD accounted for 32.55%, with only 4 cases having antecedents on both lines (9.30%). Unequivocally characterized by a vast etiology, AD is a multifactorial disorder resulting from the bilateral interaction and continuous corroboration of genetic and environmental factors. [ABSTRACT FROM AUTHOR]

The aging of populations is a global phenomenon that follows a possible increase in the incidence of neurodegenerative diseases. Alzheimer's, Parkinson's, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Huntington's diseases are some neurodegenerative disorders that aging could initiate or aggravate. Recent research has indicated that intestinal microbiota dysbiosis can trigger metabolism and brain functioning, contributing to the etiopathogenesis of those neurodegenerative diseases. The intestinal microbiota and its metabolites show significant functions in various aspects, such as the immune system modulation (development and maturation), the maintenance of the intestinal barrier integrity, the modulation of neuromuscular functions in the intestine, and the facilitation of essential metabolic processes for both the microbiota and humans. The primary evidence supporting the connection between intestinal microbiota and its metabolites with neurodegenerative diseases are epidemiological observations and animal models experimentation. This paper reviews up-to-date evidence on the correlation between the microbiota-gut-brain axis and neurodegenerative diseases, with a specially focus on gut metabolites. Dysbiosis can increase inflammatory cytokines and bacterial metabolites, altering intestinal and blood-brain barrier permeability and causing neuroinflammation, thus facilitating the pathogenesis of neurodegenerative diseases. Clinical data supporting this evidence still needs to be improved. Most of the works found are descriptive and associated with the presence of phyla or species of bacteria with neurodegenerative diseases. Despite the limitations of recent research, the potential for elucidating clinical questions that have thus far eluded clarification within prevailing pathophysiological frameworks of health and disease is promising through investigation of the interplay between the host and microbiota. [ABSTRACT FROM AUTHOR]

The amyloid-cascade-hypothesis of the pathogenesis of Alzheimer’s disease (AD) was introduced 32 years ago, in 1992. From early on, this clear and straight forward hypothesis received a lot of attention, but also a lot of substantial criticism. Foremost, there have always been massive doubts that a complex age-associated disorder of the most intricate organ of the human body, the brain, can be explained by a linear, one-dimensional cause-and-effect model. The amyloid-cascade defines the generation, aggregation, and deposition of the amyloid beta peptide as the central pathogenic mechanism in AD, as the ultimate trigger of the disease, and, consequently, as the key pharmacological target. Certainly, the original 1992 version of this hypothesis has been refined by various means, and the ‘formulating fathers’ followed up with a few reappraisals and partly very open reflections in 2002, 2006, 2009, and 2016. However, up until today, for the supporters of this hypothesis, the central and initial steps of the cascade are believed to be driven by amyloid beta—even if now displayed somewhat more elaborate. In light of the recently published clinical results achieved with anti-amyloid antibodies, the controversy in the field about (1) the clinical meaningfulness of this approach, (2) the significance of clearance of the amyloid beta peptide, and last but not least (3) the relevance of the amyloid-cascade-hypothesis is gaining momentum. This review addresses the interesting manifestation of the amyloid-cascade-hypothesis as well as its ups and downs over the decades.

Voltage-gated ion channels are essential for membrane potential maintenance, homeostasis, electrical signal production and controlling the Ca2+ flow through the membrane. Among all ion channels, the key regulators of neuronal excitability are the voltage-gated potassium channels (KV), the largest family of K+ channels. Due to the ROS high levels in the aging brain, K+ channels might be affected by oxidative agents and be key in aging and neurodegeneration processes. This review provides new insight about channelopathies in the most studied neurodegenerative disorders, such as Alzheimer Disease, Parkinson's Disease, Huntington Disease or Spinocerebellar Ataxia. The main affected KV channels in these neurodegenerative diseases are the KV1, KV2.1, KV3, KV4 and KV7. Moreover, in order to prevent or repair the development of these neurodegenerative diseases, previous KV channel modulators have been proposed as therapeutic targets. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) remains a significant health challenge, with an increasing prevalence globally. Recent research has aimed to deepen the understanding of the disease pathophysiology and to find potential therapeutic interventions. In this regard, G protein-coupled receptors (GPCRs) have emerged as novel potential therapeutic targets to palliate the progression of neurodegenerative diseases such as AD. Orexin and cannabinoid receptors are GPCRs capable of forming heteromeric complexes with a relevant role in the development of this disease. On the one hand, the hyperactivation of the orexins system has been associated with sleep–wake cycle disruption and Aβ peptide accumulation. On the other hand, cannabinoid receptor overexpression takes place in a neuroinflammatory environment, favoring neuroprotective effects. Considering the high number of interactions between cannabinoid and orexin systems that have been described, regulation of this interplay emerges as a new focus of research. In fact, in microglial primary cultures of APPSw/Ind mice model of AD there is an important increase in CB2R–OX1R complex expression, while OX1R antagonism potentiates the neuroprotective effects of CB2R. Specifically, pretreatment with the OX1R antagonist has been shown to strongly potentiate CB2R signaling in the cAMP pathway. Furthermore, the blockade of OX1R can also abolish the detrimental effects of OX1R overactivation in AD. In this sense, CB2R–OX1R becomes a new potential therapeutic target to combat AD. [ABSTRACT FROM AUTHOR]

Recent advances in neurology and biochemistry offer new hope for the prevention and treatment of mild cognitive impairment (MCI) and Alzheimer's disease (AD), through the use of antioxidants such as glutathione and plant polyphenols such as oleuropein. A recent study at the San Giovanni di Dio Institute in Rome highlighted these benefits, highlighting the key role of glutathione, a powerful intracellular antioxidant, whose concentration decreases with age and in brain areas affected by AD. Oleuropein, the main polyphenol in olive tree (Olea europaea), shows neuroprotective abilities, interfering with the accumulation of the toxic proteins amyloid and tau, which are associated with neurodegeneration. The study involved 40 patients with mild AD, divided into two groups: one received treatment with S-acetyl-glutathione, oleuropein, and vitamins for six months, while the other started treatment after six months without treatment. The results demonstrated significant improvements in the cognitive, behavioral, and executive skills of the treated patients, confirming the efficacy of this nutraceutical combination. These findings pave the way for new therapeutic protocols for neurodegenerations related to oxidative stress and protein misfolding, highlighting the importance of a preventive approach that integrates antioxidants and polyphenols into the diet, along with a healthy lifestyle, to counteract the advancement of MCI and AD. Research continues with a larger cohort of patients to confirm and expand these promising findings. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most prevalent form of neurodegeneration. Despite the well-established link between tau aggregation and clinical progression, the major pathways driven by this protein to intrinsically damage neurons are incompletely understood. To model AD-relevant neurodegeneration driven by tau, we overexpressed non-mutated human tau in primary mouse neurons and observed substantial axonal degeneration and cell death, a process accompanied by activated caspase 3. Mechanistically, we detected deformation of the nuclear envelope and increased DNA damage response in tau-expressing neurons. Gene profiling analysis further revealed significant alterations in the mitogen-activated protein kinase (MAPK) pathway; moreover, inhibitors of dual leucine zipper kinase (DLK) and c-Jun N-terminal kinase (JNK) were effective in alleviating wild-type human tau-induced neurodegeneration. In contrast, mutant P301L human tau was less toxic to neurons, despite causing comparable DNA damage. Axonal DLK activation induced by wild-type tau potentiated the impact of DNA damage response, resulting in overt neurotoxicity. In summary, we have established a cellular tauopathy model highly relevant to AD and identified a functional synergy between the DLK-MAPK axis and DNA damage response in the neuronal degenerative process. [ABSTRACT FROM AUTHOR]

Neuroprotection refers to the mechanisms and strategies used to protect the Central Nervous System (CNS) from neuronal injuries caused by neurodegenerative disorders. Neurodegenerative disorders are a type of chronic condition in which parts of the nervous system deteriorate over time, most notably the brain. These disorders have a slow and gradual effect on an individual. Neurodegeneration is a neuropathological condition and brain aging process. The brain pathology of neurodegenerative and cerebrovascular disease is a leading cause of death worldwide, with a death rate of approximately 8% and an incidence rate of approximately 2/1000. It is a major health issue in the twenty-first century. According to researchers, this disease affects over 50 million people worldwide. These disorders primarily affect people over the age of 65, and the World Health Organization predicts that this number will more than double in the next 30 years. Confusion, difficulty thinking, pain, muscle spasms, behavioral changes, paralysis, tremors, balance problems, coordination issues, hunched posture, and fatigue are symptoms of these disorders. These disorders are caused by age, genetics, medical history, habits, routine, and environment. This review article is focused on herbs such as Crocus sativus and Curcuma longa which are very helpful in Neurodegenerative diseases and serve as a resource for future research. [ABSTRACT FROM AUTHOR]

Copyright of Kranion is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Gaceta Médica de Caracas is the property of Academia Nacional de Medicina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Recent research from many Arabic-speaking countries indicates that the aging population is more prone to certain neurodegenerative diseases. This increased vulnerability implies exploring the specific needs and challenges faced by individuals with dementia within these communities. Neurocognitive interventions and assessment-based protocols for dementia have recently shifted from a disease-centered approach to a person-centered care model, which recognizes people with dementia as psychosocial individuals who live and interact in a particular sociocultural and linguistic context. This shifting paradigm embraces a more holistic approach, acknowledging the significant impact of their psychosocial functioning as well as their experience of the disease. In this context, we provide an overview of dementia in Arabic-speaking people with Alzheimer's disease, with a focus on sociolinguistic and sociocultural profiles. We detail the cultural aspects that should be incorporated into cognitive testing and care for their home or host countries if they are migrants. We discuss the limits of diagnosis, neurocognitive testing, and therapeutic interventions in this context. We formulate a set of recommendations for clinicians dealing with neurocognitive disorders, related to the acculturation and diglossic differences between the dialect spoken by the clinician and the client. However, limited access to interpreters and the lack of adapted resources can reveal deeper issues which require systemic solutions. Therefore, clinicians should be aware of cultural differences in language, culture, and country of origin. Many so-called "ethnic, translinguistic, and diglossic misunderstandings" are linked to poor linguistic comprehension, language barriers, and illiteracy. [ABSTRACT FROM AUTHOR]

The acidic pH of lysosomes is critical for catabolism in eukaryotic cells and is altered in neurodegenerative disease including Alzheimer and Parkinson. Recent reports using Drosophila and mammalian cell culture systems have identified novel and, at first sight, conflicting roles for the lysosomal associated membrane proteins (LAMPs) in the regulation of the endolysosomal system. Abbreviation: AD: Alzheimer disease; LAMP: lysosomal associated membrane protein; LTR: LysoTracker; PD: Parkinson disease; TMEM175: transmembrane protein 175; V-ATPase: vacuolar-type H+-translocating ATPase [ABSTRACT FROM AUTHOR]

Background: Digital neuropsychological tools for diagnosing neurodegenerative diseases in the older population are becoming more relevant and widely adopted because of their diagnostic capabilities. In this context, explicit memory is mainly examined. The assessment of implicit memory occurs to a lesser extent. A common measure for this assessment is the serial reaction time task (SRTT). Objective: This study aims to develop and empirically test a digital tablet–based SRTT in older participants with cognitive impairment (CoI) and healthy control (HC) participants. On the basis of the parameters of response accuracy, reaction time, and learning curve, we measure implicit learning and compare the HC and CoI groups. Methods: A total of 45 individuals (n=27, 60% HCs and n=18, 40% participants with CoI—diagnosed by an interdisciplinary team) completed a tablet-based SRTT. They were presented with 4 blocks of stimuli in sequence and a fifth block that consisted of stimuli appearing in random order. Statistical and machine learning modeling approaches were used to investigate how healthy individuals and individuals with CoI differed in their task performance and implicit learning. Results: Linear mixed-effects models showed that individuals with CoI had significantly higher error rates (b=−3.64, SE 0.86; z =−4.25; P <.001); higher reaction times (F 1,41=22.32; P <.001); and lower implicit learning, measured via the response increase between sequence blocks and the random block (β=−0.34; SE 0.12; t =−2.81; P =.007). Furthermore, machine learning models based on these findings were able to reliably and accurately predict whether an individual was in the HC or CoI group, with an average prediction accuracy of 77.13% (95% CI 74.67%-81.33%). Conclusions: Our results showed that the HC and CoI groups differed substantially in their performance in the SRTT. This highlights the promising potential of implicit learning paradigms in the detection of CoI. The short testing paradigm based on these results is easy to use in clinical practice. [ABSTRACT FROM AUTHOR]

Metformin, a widely prescribed medication for type 2 diabetes, has garnered increasing attention for its potential neuroprotective properties due to the growing demand for treatments for Alzheimer's, Parkinson's, and motor neuron diseases. This review synthesizes experimental and clinical studies on metformin's mechanisms of action and potential therapeutic benefits for neurodegenerative disorders. A comprehensive search of electronic databases, including PubMed, MEDLINE, Embase, and Cochrane library, focused on key phrases such as "metformin", "neuroprotection", and "neurodegenerative diseases", with data up to September 2023. Recent research on metformin's glucoregulatory mechanisms reveals new molecular targets, including the activation of the LKB1–AMPK signaling pathway, which is crucial for chronic administration of metformin. The pleiotropic impact may involve other stress kinases that are acutely activated. The precise role of respiratory chain complexes (I and IV), of the mitochondrial targets, or of the lysosomes in metformin effects remains to be established by further research. Research on extrahepatic targets like the gut and microbiota, as well as its antioxidant and immunomodulatory properties, is crucial for understanding neurodegenerative disorders. Experimental data on animal models shows promising results, but clinical studies are inconclusive. Understanding the molecular targets and mechanisms of its effects could help design clinical trials to explore and, hopefully, prove its therapeutic effects in neurodegenerative conditions. [ABSTRACT FROM AUTHOR]

Dihydrolipoic acid (DHLA) is a natural antioxidant known for its ability to counteract metal toxicity and oxidative stress. It has shown the potential to safeguard cells from harmful environmental substances. It may hold therapeutic benefits in treating neurodegenerative disorders by defending against oxidative damage and chronic inflammation. Thus, this study aimed to explore the potential neuroprotective effects of DHLA against aluminum (Al)‐induced toxicity using an Alzheimer's disease (AD) model in vitro. The study focused on two important pathways: GSK‐3β and the Wnt signaling pathways. The SH‐SY5Y cell line was differentiated to establish AD, and the study group were as follows: control, Al, DHLA, Al‐DHLA, AD, AD‐Al, AD‐DHLA, and AD‐Al‐DHLA. The impact of DHLA on parameters related to oxidative stress was assessed. The activity of the GSK‐3β pathway was measured by evaluating the levels of PPP1CA, PP2A, GSK‐3β, and Akt. The Wnt signaling pathway was assessed by measuring Wnt/β‐catenin in the different study groups. Exposure to DHLA significantly reduced oxidative stress by effectively decreasing the levels of reactive oxygen species, thereby protecting against protein oxidation and limiting the production of malonaldehyde. Moreover, the DHLA‐treated groups exhibited a remarkable increase in the total antioxidant capacity. Furthermore, the study observed an upregulation of the Wnt signaling pathway and a downregulation of the GSK‐3β pathway in the groups treated with DHLA. In summary, the neuroprotective effects of DHLA, primarily achieved by reducing oxidative stress and modulating critical imbalanced pathways associated with AD, indicate its potential as a promising addition to the treatment regimens of AD patients. The use of DHLA treatment has a notable effect on decreasing oxidative stress, providing protection against protein oxidation, and enhancing the overall antioxidant capacity. Additionally, DHLA treatment results in the activation of the Wnt signaling pathway and the suppression of the GSK‐3β pathway. These discoveries indicate that DHLA holds promise as a valuable supplement in the treatment of AD by mitigating oxidative stress and regulating imbalanced pathways linked to the disease. [ABSTRACT FROM AUTHOR]

The occurrence of significant Alzheimer's disease (AD) pathology was described in approximately 30% of normal pressure hydrocephalus (NPH) cases, leading to the distinction between neurodegenerative and idiopathic forms of this disorder. Whether or not there is a specific MRI signature of NPH remains a matter of debate. The present study focuses on asymptomatic cases at risk for NPH as defined with automatic machine learning tools and combines automatic MRI assessment of cortical and white matter volumetry, risk of AD (AD-RAI), and brain age gap estimation (BrainAge). Our hypothesis was that brain aging and AD process-independent volumetric changes occur in asymptomatic NPH-positive cases. We explored the volumetric changes in normal aging-sensitive (entorhinal cortex and parahippocampal gyrus/PHG) and AD-signature areas (hippocampus), four control cortical areas (frontal, parietal, occipital, and temporal), and cerebral and cerebellar white matter in 30 asymptomatic cases at risk for NPH (NPH probability >30) compared to 30 NPH-negative cases (NPH probability <5) with preserved cognition. In univariate regression models, NPH positivity was associated with decreased volumes in the hippocampus, parahippocampal gyrus (PHG), and entorhinal cortex bilaterally. The strongest negative association was found in the left hippocampus that persisted when adjusting for AD-RAI and Brain Age values. A combined model including the three parameters explained 36.5% of the variance, left hippocampal volumes, and BrainAge values, which remained independent predictors of the NPH status. Bilateral PHG and entorhinal cortex volumes were negatively associated with NPH-positive status in univariate models but this relationship did not persist when adjusting for BrainAge, the latter remaining the only predictor of the NPH status. We also found a negative association between bilateral cerebral and cerebellar white matter volumes and NPH status that persisted after controlling for AD-RAI or Brain Age values, explaining between 50 and 65% of its variance. These observations support the idea that in cases at risk for NPH, as defined by support vector machine assessment of NPH-related MRI markers, brain aging-related and brain aging and AD-independent volumetric changes coexist. The latter concerns volume loss in restricted hippocampal and white matter areas that could be considered as the MRI signature of idiopathic forms of NPH. [ABSTRACT FROM AUTHOR]

Alzheimer's Disease (AD), which is quite prevalent in our society, not only makes the lives of patients and their families more challenging but also brings significant economic burdens. Sideritis species are widely used in folk medicine due to their various effects such as anti-inflammatory, antimicrobial, diuretic, and antispasmodic properties. Although there are many studies with the hypothesis that ROS is effective in the pathogenesis of neurodegenerative diseases, there are not enough studies on Sideritis germanicopolitana Bornm. subsp. viridis Hausskn. ex Bornm. (SGV) and Sideritis libanotica Labill. subsp. linearis (Bentham) Bornm. (SLL) species. In this study, the antioxidant activities of SGV and SLL plant extracts were compared using DPPH, FRAP, and CUPRAC methods to aid in AD treatment research. It was determined that SGV extract has higher DPPH (0.023±0.005 mg/mL), FRAP (1.074± 0.180 mM FeSO4/mg extract) and CUPRAC (2,988± 0,041 mM trolox equivalent/mg extract) activity potential than SLL extract. Additionally, as a result of cytotoxicity studies performed on SH-SY5Y neuroblastoma cells, ethanol extracts of SGV may be more suitable for use in AD at higher concentrations (250 µg/mL). [ABSTRACT FROM AUTHOR]

Memory dysfunction is a neurodegenerative disorder in which a person loses his memory, where AD (Alzheimer's disease) is appraised as the major trigger of it. Today, everyday consumption of coffee has become a modern lifestyle, and this culture has gained more attention to the researchers. In this study, the potentiality of Coffea robusta and its bioactive compounds in memory function are presented. The latest articles (2018 to 2023) from databases (Scopus, Google Scholar and PubMed) were screened and 120 references were selected for this review. The major keywords for searching were "Coffee", "Coffea robusta", "bioactive compounds", "memory dysfunction" and "Alzheimer's disease". For the improvement of memory function, C. robusta and its bioactive compounds, such as caffeine acts as antioxidant and its major targets are adenosine receptors while chlorogenic acid reduces amyloid ß (Aß) deposition, neo and crypto-chlorogenic acid scavenge reactive oxygen species (ROS) in neuronal cells, moreover, trigonelline prevents neuronal injury by bringing down astrocyte activity, and antioxidant activity of melanoidins (especially interfering redox-sensitive transcription factors) contribute to their beneficial effects in AD and impart neuroprotection as well as increase memory function. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases affect millions of people worldwide. The failure of the enzymatic degradation, the oxidative stress, the dyshomeostasis of metal ions, among many other biochemical events, might trigger the pathological route, but the onset of these pathologies is unknown. Multi-target and multifunctional molecules could address several biomolecular issues of the pathologies. The tripeptide GHK, a bioactive fragment of several proteins, and the related copper(II) complex have been largely used for many purposes, from cosmetic to therapeutic applications. GHK derivatives were synthesized to increase the peptide stability and improve the target delivery. Herein we report the synthesis of a new biotin–GHK conjugate (BioGHK) through orthogonal reactions. BioGHK is still capable of coordinating copper(II), as observed by spectroscopic and spectrometric measurements. The spectroscopic monitoring of the copper-induced ascorbate oxidation was used to measure the antioxidant activity Cu(II)-BioGHK complex, whereas antiglycant activity of the ligand towards harmful reactive species was investigated using MALDI-TOF. The affinity of BioGHK for streptavidin was evaluated using a spectrophotometric assay and compared to that of biotin. Finally, the antiaggregant activity towards amyloid-β was evaluated using a turn-on fluorescent dye. BioGHK could treat and/or prevent several adverse biochemical reactions that characterize neurodegenerative disorders, such as Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The current literature review aimed to evaluate the effectiveness of rTMS on the precuneus as a potential treatment for Alzheimer's disease (AD). Although the number of studies specifically targeting the precuneus is limited, the results from this review suggest the potential benefits of this approach. Future studies should focus on exploring the long-term effects of rTMS on the precuneus in Alzheimer's disease patients, as well as determining the optimal stimulation parameters and protocols for this population. Additionally, investigating the effects of rTMS on the precuneus in combination with other brain regions implicated in AD may provide valuable insights into the development of effective treatment for this debilitating neurodegenerative disorder. [ABSTRACT FROM AUTHOR]

Introduction: Published data obtained from in vitro and in vivo studies was reviewed systematically and analyzed critically to evaluate the effect of oral cavity-derived stem cells (OCDSCs) on the recovery or therapy of neurodegenerative diseases (NDs), such as Alzheimer disease (AD), amyotrophic lateral sclerosis (ALS), Huntington (HD) diseases, and Parkinson disease (PD). Methods: An electronic search was accomplished. References of included articles were also manually searched. Studies were critically evaluated for suitability against the inclusion/ exclusion criteria and the data was extracted. Bias risk evaluation of the studies and evidence synthesis were conducted. Results: A total of 14 in vivo and 10 in vitro studies met the inclusion criteria. PD was induced in 10 in vivo and 7 in vitro studies, while AD was induced in 2 in vivo and 4 in vitro studies. Two studies (1 in vitro and 1 in vivo) evaluated ALS disease and 1 in vivo study evaluated HD. Moderate evidence was found for in vitro studies reporting the positive effect of OCDSCs on PD or AD recovery. Strong evidence was found for in vivo studies in which PD animal models were used; meanwhile, moderate evidence was found for the impact of OCDSCs on AD recovery. Limited evidence was found for in vivo studies evaluating HD and ALS. Conclusion: Although studies reported favorable data regarding the OCDSCs on NDs, they presented a considerable risk of bias. Because of heterogeneous study characteristics, the current study recommends improving standardized methods to evaluate the therapeutic effects of OCDSCs on the NDs. [ABSTRACT FROM AUTHOR]

In light of the rising evidence of the association between viral and bacterial infections and neurodegeneration, we aimed at revisiting the infectious hypothesis of Alzheimer’s disease and analyzing the possible implications of COVID-19 neurological sequelae in long-term neurodegeneration. We wondered how SARS-CoV-2 could be related to the amyloid-β cascade and how it could lead to the pathological hallmarks of the disease. We also predict a paradigm change in clinical medicine, which now has a great opportunity to conduct prospective surveillance of cognitive sequelae and progression to dementia in people who suffered severe infections together with other risk factors for Alzheimer’s disease.

Physical activity (PA), which includes exercise, can reduce the risk of developing various non-communicable diseases, including neurodegenerative diseases (NDs), and mitigate their adverse effects. However, the mechanisms underlying this ability are not yet fully understood. Among several possible mechanisms proposed, such as the stimulation of brain-derived neurotrophic factor (BDNF), endothelial nitric oxide synthase (eNOS), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), the possible involvement of particular vesicular structures enclosed in lipid membranes known as extracellular vesicles (EVs) has recently been investigated. These EVs would appear to exert a paracrine and systemic action through their ability to carry various molecules, particularly so-called microRNAs (miRNAs), performing a function as mediators of intercellular communication. Interestingly, EVs and miRNAs are differentially expressed following PA, but evidence on how different exercise parameters may differentially affect EVs and the miRNAs they carry is still scarce. In this review we summarized the current human findings on the effects of PA and different exercise parameters exerted on EVs and their cargo, focusing on miRNAs molecules, and discussing how this may represent one of the biological mechanisms through which exercise contributes to preventing and slowing NDs. [ABSTRACT FROM AUTHOR]

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Alzheimer's disease (AD) is characterized mainly by the accumulation of Amyloid-β oligomers (Aβo) in the brain that leads to hyperphosphorylation and polymerization of the Tau protein in neurofibrillary tangles, which is associated with neuronal death. The initial stage of the disease is due to the production and accumulation of Aβo which is produced from the cleavage of the Amyloid-β precursor protein (APP) by the β-secretase (BACE1) enzyme. Growing evidences indicate that the cellular prion (PrPc) can restrict the activity of BACE1 and, therefore, interrupt the production and toxicity of Aβo. Studies also suggest that the Aβo-PrPc interaction is necessary to trigger the synaptotoxic effects, which depend on the Aβo stimulus. Here we presented an in-depth review of PrPc and its involvement with AD to understand if PrPc can be a marker or target in AD.

A growing number of studies is focusing on the pharmacology and feasibility of bioactive compounds as a novel valuable approach to target a variety of human diseases related to neurological degeneration. Among the group of the so-called medicinal mushrooms (MMs), Hericium erinaceus has become one of the most promising candidates. In fact, some of the bioactive compounds extracted from H. erinaceus have been shown to recover, or at least ameliorate, a wide range of pathological brain conditions such as Alzheimer's disease, depression, Parkinson's disease, and spinal cord injury. In a large body of in vitro and in vivo preclinical studies on the central nervous system (CNS), the effects of erinacines have been correlated with a significant increase in the production of neurotrophic factors. Despite the promising outcome of preclinical investigations, only a limited number of clinical trials have been carried out so far in different neurological conditions. In this survey, we summarized the current state of knowledge on H. erinaceus dietary supplementation and its therapeutic potential in clinical settings. The bulk collected evidence underlies the urgent need to carry out further/wider clinical trials to prove the safety and efficacy of H. erinaceus supplementation, offering significant neuroprotective applications in brain pathologies. [ABSTRACT FROM AUTHOR]

When treating structured health-system-related knowledge, the establishment of an over-dimension to guide the separation of entities becomes essential. This is consistent with the information retrieval processes aimed at defining a coherent and dynamic way - meaning by that the multilevel integration of medical textual inputs and computational interpretation - to replicate the flow of data inserted in the clinical records. This study presents a strategic technique to categorize the clinical entities related to patients affected by neurodegenerative diseases. After a pre-processing range of tasks over paper-based and handwritten medical records, and through subsequent machine learning and, more specifically, natural language processing operations over the digitized clinical records, the research activity provides a semantic support system to detect the main symptoms and locate them in the appropriate clusters. Finally, the supervision of the experts proved to be essential in the correspondence sequence configuration aimed at providing an automatic reading of the clinical records according to the clinical data that is needed to predict the detection of neurodegenerative disease symptoms. [ABSTRACT FROM AUTHOR]

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In this case-control study, we evaluated the association between serum antibodies against hepatitis E virus (HEV) and central nervous system (CNS) neurodegenerative disorders (NDs) in older people with dementia. The presence of anti-HEV antibodies was related to a higher adjusted odds ratio (aOR) of having CNS NDs by neuropathological diagnosis (aOR, 2.13; P =.007) and clinical/neuropathological diagnosis (1.84; P =.02). Besides, serum anti-HEV antibodies were directly related to neuropathological injury (higher vascular pathology [aOR, 1.97; P =.006]) and higher probability of Alzheimer-type pathology (1.84; P =.02). In conclusion, the presence of anti-HEV antibodies was related to higher odds of CNS NDs and neuropathological injury in older people. [ABSTRACT FROM AUTHOR]

Creating a cellular model of Alzheimer's disease (AD) that accurately recapitulates disease pathology has been a longstanding challenge. Recent studies showed that human AD neural cells, integrated into three-dimensional (3D) hydrogel matrix, display key features of AD neuropathology. Like in the human brain, the extracellular matrix (ECM) plays a critical role in determining the rate of neuropathogenesis in hydrogel-based 3D cellular models. Aging, the greatest risk factor for AD, significantly alters brain ECM properties. Therefore, it is important to understand how age-associated changes in ECM affect accumulation of pathogenic molecules, neuroinflammation, and neurodegeneration in AD patients and in vitro models. In this review, mechanistic hypotheses is presented to address the impact of the ECM properties and their changes with aging on AD and AD-related dementias. Altered ECM characteristics in aged brains, including matrix stiffness, pore size, and composition, will contribute to disease pathogenesis by modulating the accumulation, propagation, and spreading of pathogenic molecules of AD. Emerging hydrogel-based disease models with differing ECM properties provide an exciting opportunity to study the impact of brain ECM aging on AD pathogenesis, providing novel mechanistic insights. Understanding the role of ECM aging in AD pathogenesis should also improve modeling AD in 3D hydrogel systems. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDDs) are a major health problem worldwide. Statistics suggest that in America in 2030 there will be more than 12 million people suffering from a neurodegenerative pathology. Furthermore, the increase in life expectancy enhances the importance of finding new and better therapies for these pathologies. NDDs could be classified into chronic or acute, depending on the time required for the development of clinical symptoms and brain degeneration. Nevertheless, both chronic and acute stages share a common immune and inflammatory pathway in their pathophysiology. Immunization with neural-derived peptides (INDP) is a novel therapy that has been studied during the last decade. By inoculating neural-derived peptides obtained from the central nervous system (CNS), this therapy aims to boost protective autoimmunity, an autoreactive response that leads to a protective phenotype that produces a healing environment and neuroregeneration instead of causing damage. INDP has shown promising findings in studies performed either in vitro, in vivo or even in some pre-clinical trials of different NDDs, standing as a potentially beneficial therapy. In this review, we will describe some of the studies in which the effect of INDP strategies have been explored in different (chronic and acute) neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Liquid-liquid phase separation (LLPS) is a critical phenomenon that leads to the formation of liquid-like membrane-less organelles within cells. Advances in our understanding of condensates reveal their significant roles in biology and highlight how their dysregulation may contribute to disease. Recent evidence indicates that the high protein concentration in coacervates may lead to abnormal protein aggregation associated with several neurodegenerative diseases. The presence of condensates containing multiple amyloidogenic proteins may play a role in the co-deposition and comorbidity seen in neurodegeneration. This review first provides a brief overview of the physicochemical bases and molecular determinants of LLPS. It then summarizes our understanding of Tau and α-synuclein (AS) phase separation, key proteins in Alzheimer's and Parkinson's diseases. By integrating recent findings on complex Tau and AS coacervation, this article offers a fresh perspective on how LLPS may contribute to the pathological overlap in neurodegenerative disorders and provide a novel therapeutic target to mitigate or prevent such conditions. [Display omitted] • LLPS forms dynamic condensates that organize cellular biochemistry. • Intrinsically disordered proteins are key players in LLPS and neurodegenerative diseases. • Abnormal LLPS may lead to protein aggregation, influencing disease pathology. • LLPS may facilitate the pathological overlap of α-synuclein and Tau in neurodegeneration. • Understanding LLPS can reveal new therapeutic targets for overlapping neuropathies. [ABSTRACT FROM AUTHOR]

Over the past century, advances in biotechnology, biochemistry, and pharmacognosy have spotlighted flavonoids, polyphenolic secondary metabolites that have the ability to modulate many pathways involved in various biological mechanisms, including those involved in neuronal plasticity, learning, and memory. Moreover, flavonoids are known to impact the biological processes involved in developing neurodegenerative diseases, namely oxidative stress, neuroinflammation, and mitochondrial dysfunction. Thus, several flavonoids could be used as adjuvants to prevent and counteract neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Zebrafish is an interesting model organism that can offer new opportunities to study the beneficial effects of flavonoids on neurodegenerative diseases. Indeed, the high genome homology of 70% to humans, the brain organization largely similar to the human brain as well as the similar neuroanatomical and neurochemical processes, and the high neurogenic activity maintained in the adult brain makes zebrafish a valuable model for the study of human neurodegenerative diseases and deciphering the impact of flavonoids on those disorders. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a neurodegenerative disease characterized by the formation of amyloid plaques constituted prevalently by amyloid peptides. Due to the well-known challenges related to the study in solution of these peptides, several membrane-mimicking systems such as micelle constituted by detergent—i.e., DPC and SDS—have been deeply investigated. Additionally, the strategy of studying short fragments instead of the full-length peptide turned out to be advantageous in exploring the structural properties of the different moieties in Aβ in order to reproduce its pathologic effects. Several studies reveal that among Aβ fragments, Aβ(25−35) is the shortest fragment able to reproduce the aggregation process. To enrich the structural data currently available, in the present work we decided to evaluate the conformational changes adopted by Aβ(25−35) in SDS combining CD and NMR spectroscopies at different times. From the solved structures, it emerges that Aβ(25−35) passes from an unordered conformation at the time of the constitution of the system to a more ordered and energetically favorable secondary structure at day 7, which is kept for 2 weeks. These preliminary data suggest that a relatively long time affects the kinetic in the aggregation process of Aβ(25−35) in a micellar system, favoring the stabilization and the formation of a soluble helix conformation. [ABSTRACT FROM AUTHOR]

Background: In the older general population, neurodegenerative diseases (NDs) are associated with increased disability, decreased physical and cognitive function. Detecting risk factors can help implement prevention measures. Using deep neural networks (DNNs), a machine-learning algorithm could be an alternative to Cox regression in tabular datasets with many predictive features. We aimed to compare the performance of different types of DNNs with regularized Cox proportional hazards models to predict NDs in the older general population. Methods: We performed a longitudinal analysis with participants of the English Longitudinal Study of Ageing. We included men and women with no NDs at baseline, aged 60 years and older, assessed every 2 years from 2004 to 2005 (wave2) to 2016–2017 (wave 8). The features were a set of 91 epidemiological and clinical baseline variables. The outcome was new events of Parkinson's, Alzheimer or dementia. After applying multiple imputations, we trained three DNN algorithms: Feedforward, TabTransformer, and Dense Convolutional (Densenet). In addition, we trained two algorithms based on Cox models: Elastic Net regularization (CoxEn) and selected features (CoxSf). Results: 5433 participants were included in wave 2. During follow-up, 12.7% participants developed NDs. Although the five models predicted NDs events, the discriminative ability was superior using TabTransformer (Uno's C-statistic (coefficient (95% confidence intervals)) 0.757 (0.702, 0.805). TabTransformer showed superior time-dependent balanced accuracy (0.834 (0.779, 0.889)) and specificity (0.855 (0.0.773, 0.909)) than the other models. With the CoxSf (hazard ratio (95% confidence intervals)), age (10.0 (6.9, 14.7)), poor hearing (1.3 (1.1, 1.5)) and weight loss 1.3 (1.1, 1.6)) were associated with a higher DNN risk. In contrast, executive function (0.3 (0.2, 0.6)), memory (0, 0, 0.1)), increased gait speed (0.2, (0.1, 0.4)), vigorous physical activity (0.7, 0.6, 0.9)) and higher BMI (0.4 (0.2, 0.8)) were associated with a lower DNN risk. Conclusion: TabTransformer is promising for prediction of NDs with heterogeneous tabular datasets with numerous features. Moreover, it can handle censored data. However, Cox models perform well and are easier to interpret than DNNs. Therefore, they are still a good choice for NDs. [ABSTRACT FROM AUTHOR]