alzheimer’s disease

The global rise of obesity has increased the prevalence of type 2 diabetes mellitus (T2DM) and the risk of Alzheimer’s disease (AD). The obesity, a key risk factor of T2DM, leads to insulin resistance, which contributes to cognitive decline and potentially AD through shared metabolic pathways. This Commentary highlights the connection between obesity, T2DM, and AD, suggesting that lifestyle changes like weight loss and discontinuation of sugar consumption may help to prevent these conditions. Comprehensive public health strategies focusing on diet, exercise, and education are essential to reduce the growing health crisis and improve metabolic and cognitive health globally.

This review synthesizes and elaborates on current studies examining the neurotoxic effects of microplastics, emphasizing their mechanisms of entry into the central nervous system and their possible involvement in the development of neurodegenerative disorders. The pervasive presence of microplastics in the environment has heightened concerns about their accumulation in biological systems, particularly their capacity to traverse biological boundaries and engage with neuronal tissues. This article seeks to synthesize and critically evaluate the existing scientific literature on microplastic neuroinvasion, concentrating on the mechanisms through which these particles penetrate the blood-brain barrier (BBB) specifically via transcellular, paracellular, or Trojan horse pathways—and their ensuing effects on neuronal homeostasis.We investigate the physiological and molecular reactions triggered by microplastics, encompassing oxidative stress induction, mitochondrial failure, neuroinflammation, and synaptic disruption. These pathogenic processes may facilitate the onset and advancement of several neurodegenerative disorders, including Alzheimer’s disease, by intensifying amyloid-beta aggregation, tau phosphorylation, and neuroimmune activation. Additionally, we examine the burgeoning epidemiological and experimental evidence associating microplastic exposure with cognitive deterioration and neuronal impairment.This review offers a thorough analysis of microplastic neurotoxicity by evaluating both in vitro and in vivo studies, with the objective of elucidating the potential neurological hazards associated with these environmental contaminants. We emphasize significant deficiencies in existing research and propose future avenues, encompassing enhanced detection techniques, public health initiatives, and efforts to reduce human exposure to microplastics.

Dementia is an umbrella term describing different types of diseases that lead to cognitive impairment and memory dysfunction, predominantly affecting older adults. The most common forms include Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Despite extensive research, there is no definitive cure for dementia, primarily due to its complex and multifactorial nature, particularly the role of genetic abnormalities. Gene therapy, a novel therapeutic approach, aims to correct defective genes or introduce functional gene products by delivering specific DNA sequences to patients, and is often considered for individuals unresponsive to conventional treatments, such as those with dementia. Over the past decade, significant research has explored the potential of gene therapy in dementia, offering new hope for more effective treatments. However, several challenges remain in its practical application. One key challenge is developing safe and efficient gene delivery methods, as the brain's intricate structure and protective barriers present significant obstacles. Furthermore, ensuring the long-term expression and stability of therapeutic genes is crucial for sustained benefit. Future studies should focus on identifying genes implicated in different types of dementia, optimizing gene delivery systems, improving gene-targeting specificity, and conducting comprehensive clinical trials to assess the safety and efficacy of these therapies. Addressing these challenges could pave the way for novel treatment strategies, ultimately improving the quality of life for individuals with dementia.

The cholinergic system plays a crucial role in CNS modulation, where dysfunctions are linked to cognitive and motor impairments. Cholinesterases (ChEs), essential enzymes for synaptic transmission in the CNS, are key therapeutic targets for neurodegenerative diseases. Moreover, these conditions feature elevated reactive oxygen species that compromise cellular integrity, leading to neuronal death. This study investigated the neuroprotective effects of Salvia aristata essential oilfocusing on its phytochemical composition and ChE inhibitory properties.

The essential oil of S. aristata was extracted via hydrodistillation method and its chemical composition was analyzed by GC-MS. The ChE inhibitory effects were assessed using the modified Ellman’s method. Cell viability and neuroprotective effects of the essential oil were evaluated on PC12 cells under H₂O₂-induced oxidative stress by AlamarBlue assay.

analysis identified 74 compounds, primarily sesquiterpene hydrocarbons (32.79%), with β-trans-caryophyllene (8.37%), caryophyllene oxide (8.26%), and bicyclogermacrene (5.73%) as the major components. The essential oil showed more potent butyrylcholinesterase (BChE) inhibitory activity (IC50 = 2.72 ± 0.21 µg/mL) than anti-acetylcholinesterase activity. Based on kinetic analysis, it exhibited a mixed-type inhibition against BChE (Ki = 4.81, Kis = 3.39 µg/mL). Additionally, it effectively protected PC12 cells against H₂O₂-induced oxidative stress (p<0.001).

The essential oil of S. aristata exhibited selective BChE inhibition and significant neuroprotective effects against oxidative stress in PC12 cells. These bioactivities, likely driven by major compounds like β-trans-caryophyllene, support the potential therapeutic use of the essential oil as a neuroprotective agent. However, further in vivo and clinical studies are suggested.

The prevalence of neurodegenerative diseases such as Alzheimer's disease (AD) has increased in recent years and put additional strain on the health systems of most countries. Although great progress has been made in the treatment of these diseases, so far no effective treatment has been found that can block the progression of these diseases. In recent years, there have been reports of inhibition of hyperphosphorylation of Tau protein by extracts or natural compounds derived from medicinal plants. In this review article, we tried to review some of the medicinal plants that have shown these effects in electronic databases. Some medicinal plants including Curcuma longa, Rosmarinus officinalis, Vitis vinifera, Apocynum venetum, Centella asiatica, Rhus succedanea, Maclura pomifera Allium sativum and Ginkgo biloba have been found to show anti-Tau hyperphosphorylation effects and therefore can be considered as adjuvant therapy in Alzheimer disease (AD). The essential oils or natural product of some medicinal plant inhibited the Tau hyperphosphorylation in studies and as results are suitable options in treatments of neurodegenerative diseases including AD.

Context: 

Pesticides are widely used in agriculture and household settings and have been associated with various adverse health effects, including a potential link to neurodegenerative diseases (NDs). Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common disorders in this category, characterized by progressive neuronal cell loss and severe impairments in human functioning. Epidemiological studies have shown significant associations between pesticide exposure—specifically organochlorines, organophosphates (OP), carbamates, DDT, and paraquat—and AD and PD; however, little is known about the underlying biological mechanisms.

Evidence Acquisition: 

A mini-review was conducted in the scientific literature on the biological mechanisms linking pesticide exposure to NDs using scientific databases (PubMed, Scopus, Web of Science, and Google Scholar).

In AD, the connection may involve several biological mechanisms, including hyperphosphorylation of tau protein, which disrupts normal cellular function and contributes to neurofibrillary tangles. Genetic polymorphisms in microtubule-associated protein tau (MAPT) can also influence an individual's susceptibility to AD by affecting tau protein interactions with microtubules. Moreover, exposure to pesticides has been linked to elevated pro-inflammatory markers that exacerbate neuroinflammation, further contributing to neuronal damage. In PD, oxidative stress plays a crucial role by generating reactive oxygen species that damage cellular components. Mitochondrial dysfunction resulting from pesticide exposure impairs energy production in neurons, leading to cell death. Additionally, exacerbation of α-synuclein aggregation is a critical factor in PD pathology, as aggregated forms of this protein are toxic to neurons.

Given the rapid increase of pesticides in the air, water, and food, it is essential to clarify the biological mechanisms linking pesticide exposure to NDs.

Alzheimer's disease (AD) is associated with a marked reduction in brain-derived neurotrophic factor (BDNF) and fibronectin 1 (Fn1). This study investigates the effects of fisetin supplementation combined with high-intensity interval training (HIIT) on these neurogenesis markers in an aged mouse model of AD.  In this experimental study, 30 aged C57BL/6 mice (weight: 30 g) with AD were randomly assigned to one of the five groups: (1) Control, (2) AD, (3) AD + Fisetin, (4) AD + HIIT, and (5) AD + HIIT + Fisetin. Alzheimer's disease was induced in the AD groups by injecting amyloid-beta (Aβ1-42) into the hippocampus. The HIIT protocol consisted of a 10-minute warm-up at 50-55% VO2 max, followed by seven intervals, each comprising 4 minutes at 80-90% VO2 max and 3 minutes at 65-75% VO2 max. Fisetin was administered at 20 mg/kg for eight weeks. Data were analyzed using one-way ANOVA with a significance level of P ≤ 0.05.  Significant differences were observed in BDNF, Fn1, and Aβ gene expression levels across the five groups of aged mice (p < 0.001). BDNF and Fn1 expression were significantly reduced in the AD groups compared to the healthy controls (p < 0.001). However, their expression levels increased significantly in the AD + Training + Fisetin, AD + Training, and AD + Fisetin groups compared to the AD-only group (p < 0.001). The AD + Training + Fisetin group exhibited the highest expression levels, followed by the AD + Training and AD + Fisetin groups (p < 0.001). Aβ expression was significantly reduced in all intervention groups, with the AD + Training + Fisetin group showing the most substantial decrease (p < 0.001).  Combining HIIT and fisetin supplementation may promote cerebral neurogenesis in AD by reducing Aβ levels and enhancing BDNF and Fn1 gene expression. Notably, the combined intervention of HIIT and fisetin exhibits a more significant effect than either HIIT or fisetin alone, with HIIT being more effective than fisetin as a standalone treatment. Thus, the combination of HIIT and fisetin appears to be the most effective complementary approach for managing this disease.

The importance of cognitive decline has increased due to an aging population and changing lifestyles. Currently, an absolute diagnosis of Alzheimer's disease (AD) can only be determined through postmortem histopathological examination, although in vivo imaging is making strides toward this diagnosis. Upon examining the postmortem brains of AD patients, the disease is associated with neuropathological features such as the accumulation of amyloid β (Aβ) plaques, also known as senile plaques and neurofibrillary tangles (NFT) of highly phosphorylated tau in the brain. Early detection and diagnosis of AD are crucial, but current research on the effectiveness of contrast agents and molecules is limited. To address this gap, we conducted a comprehensive study on PET and SPECT imaging to evaluate the role of these agents and indicators in diagnosing the disorder.

A comprehensive search was conducted in PubMed, using the PRISMA guidelines, without any time or language restrictions. Three independent researchers reviewed the studies based on criteria, and relevant data from the included articles were extracted and analyzed.

As a result of the initial search, 172 original articles were included in the study. Finally, data from 116 studies were extracted. The most used contrast agents were [¹⁸F] fluorodeoxyglucose and its derivatives, [11C] acetate, and chemicals based on iodine, respectively. The most often employed transgenic mouse strains in the studies were APP/PS1, and 5XFAD. On average, 23 animals were used in each study. Respectively, Amyloid beta, Tau protein, Translocator protein (TSPO), Acetylcholinesterase (AChE), Monoamine oxidase B (MAO-B), and Gonadotropin-releasing hormone receptor (GnRHR) were identified the most as biomarkers in studies.

The study on PET and SPECT imaging for diagnosing AD has limitations, including the use of animal models and not evaluating the long-term effects or safety of contrast agents. Further research is needed to confirm these findings in clinical settings and assess the long-term impact of these contrast chemicals.

As there are currently no curative treatments for Alzheimer's disease (AD) and other forms of dementia, focusing on risk factor reduction and primary prevention is essential. This study aimed to explore the factors that influence the occurrence of AD in comparison to other dementias. We conducted a case-control study involving caregivers of Alzheimer's patients (n=60) and a control group of caregivers for individuals with other dementias (n=60). Participants were recruited from a hospital in Yogyakarta between January 2018 and December 31, 2023. An online questionnaire containing 62 questions was administered via Zoho Forms and analyzed using IBM SPSS Statistics 25.0. We employed chi-square tests, and logistic regression to identify factors associated with the incidence of AD relative to other dementias. Our findings indicated that an adequate dietary pattern (P=0.02; AOR=3.665; 95% CI=1.219-11.11) and age of 60 years or older (P=0.06; AOR=2.34; 95% CI=0.95-5.73) are significant risk factors for AD. Conversely, adequate sleep quality (P=0.03; AOR=0.24; 95% CI=0.07-0.87) and a history of stroke (P=0.00; AOR=0.07; 95% CI=0.02-0.26) were identified as protective factors against developing AD compared to other dementias. A poor diet can lead to systemic inflammation and oxidative stress, which may trigger neuroinflammation, including stroke. Additionally, increased tau load associated with being 60 years or older, along with poor sleep quality, can contribute to neuronal dysfunction and ultimately result in brain atrophy. This study identifies moderate dietary habits and age over 60 as risk factors for AD, while adequate sleep quality and a history of stroke serve as protective factors. The insights gained from this research may serve as foundational data for further studies and provide guidelines for preventing the onset of AD.

Alzheimer's is a neurodegenerative disorder characterized by memory impairment and learning difficulties. Alzheimer's disease is recognized as the most common cause of memory loss and dementia in middle-aged and elderly individuals, and it is the fifth leading cause of death among the elderly. Extensive research is being conducted to identify the causes and pathological mechanisms involved in this disease, as a proper understanding of these mechanisms could lead to the discovery of fundamental treatments. In this article, we have looked at some of the pathological mechanisms of this disease, which result from changes in synaptic function and functional connectivity.

Alzheimer's disease (AD) presents a significant challenge in healthcare, necessitating accurate and timely diagnosis for effective management. Resting-state functional magnetic resonance imaging (Rs-fMRI) has emerged as a valuable tool for understanding neural correlates and the early detection of AD. This article reviews recent advancements in utilizing Rs-fMRI in combination with machine learning (ML) techniques for early AD diagnosis. First, we discuss the underlying principles of Rs-fMRI, highlighting its ability to detect alterations in brain functional connectivity (FC) patterns associated with AD. We then explore the potential of ML algorithms, particularly support vector machines (SVMs), in analyzing Rs-fMRI data and discriminating between AD patients and healthy controls. We indicate the challenges and opportunities in integrating Rs-fMRI and ML, such as in data preprocessing, feature selection, and model interpretation. We also address the importance of large-scale, multi-site studies to validate the robustness and generalizability of the proposed approaches. Overall, the integration of Rs-fMRI and ML holds great promise as a non-invasive, objective, and sensitive diagnostic tool for AD, potentially enabling early detection and personalized treatment strategies. However, further studies are warranted to optimize methodologies, enhance interpretability, and facilitate clinical translation.

Today, according to various studies, the gut microbiome is closely linked to various diseases such as cardiovascular disease, metabolic disorders, and neurological disorders like Alzheimer's disease (AD).

The primary purpose of this investigation was to evaluate the quality and quantity of the gut microbiota in a mouse model of AD.

The mice were randomly divided into either an AD group injected with streptozotocin (STZ, 3 mg/kg) or a control group. After 16 - 17 days, the mice were evaluated for their memory capacity and learning, using the Morris water maze (MWM) and passive avoidance response tests. Specific primers were designed to target the 16S rRNA genes of Enterobacter , Clostridium , Lactobacillus , and Bifidobacterium species in the fecal samples of mice by real‐time PCR assay.

The MWM and passive avoidance tests confirmed that STZ caused AD in the mouse model. According to the results of real-time PCR assays, unlike Lactobacillus , Clostridium , and Enterobacter , the population of Bifidobacterium decreased significantly in mice after AD in day 28 (P < 0.05). In other words, mean difference of Bifidobacterium CFU between AD group in day 28 and control group was -5.680 (95% CI: -11.3826 to -0.0174).

Restructuring the gut microbiota using personalized dietary approaches or targeted interventions aimed at beneficial microbiota can potentially modify the composition of microbial communities and their metabolic byproducts, offering novel therapeutic possibilities for AD.

 Alzhеimеr’s disеasе (AD) is thе most prеvalеnt form of dеmеntia globally. Rеsеarch links thе incrеasе of rеactivе oxidativе spеciеs (ROS) to thе pathogеnеsis of AD; thus, this study invеstigatеd thе impact of mеthylglyoxal (MGO) on thе еxprеssion of miR-125b, miR-107, and gеnеs involvеd in oxidativе strеss signaling in SH-SY5Y cеlls.

 Thе MTT assay assеssеd MGO’s еffеcts on SH-SY5Y viability. miR-125b and miR-107 еxprеssion was analyzеd via rеal-timе PCR. Additionally, thе Human Oxidativе Strеss Pathway Plus RT2 Profilеr PCR array quantifiеd oxidativе pathway gеnе еxprеssion.

 MGO concеntrations undеr 700μM did not significantly rеducе SH–SY5Y viability. MiR-125b and miR-107 еxprеssion in SH-SY5Y cеlls incrеasеd and dеcrеasеd rеspеctivеly (P<0.05). Cеlls trеatеd with 700μM MGO еxhibitеd incrеasеd CCS, CYBB, PRDX3, SPINK1, CYGB, DHCR24 and BAG2 еxprеssion (P<0.05). Thosе trеatеd with 1400μM MGO showеd incrеasеd CCS, CYBB, PRDX3, SPINK1, DUSP1, EPHX2, EPX, FOXM1, and GPX3 еxprеssion (P<0.05).

 MGO altеrs oxidativе strеss pathway gеnе, miR-125b, and miR-107 еxprеssion in SH-SY5Y cеlls. Targеting MGO or miR-125b and miR-107 may providе novеl AD thеrapеutic stratеgiеs or improvе sеvеrе symptoms. Furthеr rеsеarch should еlucidatе thе prеcisе mеchanisms.