Molecular and Therapeutic Targets for Amyloid-beta Plaques in Alzheimer's Disease: A Review Study.

Alzheimer's disease (AD) is characterized by progressive loss of cognition and a gradual decrease in memory. Although AD is considered the most persistent form of dementia and a global concern, no complete cure or agents that can completely halt the progression of AD have been found. In the past years, significant progress has been made in understanding the cellular and molecular changes associated with AD, and numerous drug targets have been identified for the development of drugs for this disease. Amyloid-beta (Aß) plaques and neurofibrillary tangles (NFT) are the major attributes of AD. Symptomatic relief is the only possible treatment available at present and a disease-modifying drug is of utmost importance. The development of drugs that can inhibit different targets responsible for the formation of plaques is a potential area in AD research. This review is not a complete list of all possible targets for AD but serves to highlight the targets related to Aß pathology and pathways concerned with the formation of Aß fragments. This shall serve as a prospect in the identification of Aß plaque inhibitors and pave the strategies for newer drug treatments. Nevertheless, substantial research is done in this area but to bridle, the clinical difficulty remains a concern.

Advancing Alzheimer's Research With Zebrafish Models: Current Insights, Addressing Challenges, and Charting Future Courses.

Alzheimer's disease (AD) is a neurological condition that progressively impairs cognitive function and results in memory loss. Despite substantial research efforts, little is known about the specific processes driving AD, and there are few proven therapies. Because of their physiological and genetic resemblance to humans, zebrafish (Danio rerio) have become an important model organism for furthering research on AD. This abstract discusses the difficulties faced, looks at the insights currently garnered from zebrafish models, and suggests future research options. AD knowledge has greatly benefited from the use of zebrafish models. Transgenic zebrafish that express human AD-associated genes, such as tau and amyloid precursor protein (APP), display tau neurofibrillary tangles (NFTs) and amyloid-beta (Aß) plaques, two of the disease's main clinical characteristics. These models have clarified the roles of oxidative stress, inflammation, and calcium homeostasis in the course of AD and allowed for the purpose of high-throughput screening of potential therapeutic agents. Understanding the growth and deterioration of neurons has been greatly aided by real-time zebrafish imaging. Fully using zebrafish models in AD research requires addressing a number of issues. The dissimilarities in zebrafish anatomy and physiology from humans, the difficulty of developing models that replicate progressive and late-onset AD (LOAD), and the requirement for standardized procedures to evaluate alterations in zebrafish cognition and behavior are a few issues. Furthermore, variations in the genetic makeup of zebrafish strains might affect the results of experiments. Future directions include developing standardized behavioral assays and cognitive tests, working together to create extensive databases of zebrafish genetic and phenotypic data, and using genetic engineering techniques like CRISPR/Cas9 to create more complex zebrafish models. Combining zebrafish models with other model species helps expedite the conversion of research results into therapeutic applications and offers a more thorough knowledge of AD. To sum up, zebrafish models have made a substantial contribution to Alzheimer's research by offering insightful information on the causes of the illness and possible therapies. By tackling present issues and formulating a planned future path, we can improve the use of zebrafish to decipher the mysteries of Alzheimer's and help create successful treatments.

A Review of the Retinal Impact of Traumatic Brain Injury and Alzheimer's Disease: Exploring Inflammasome Complexes and Nerve Fiber Layer Alterations.

A huge number of new cases - around a few million of traumatic brain injury (TBI) - are recorded globally each year, making it a major public health risk. A significant portion of all accident-related deaths are attributable to TBI, a notable mortality rate. There are TBI deaths in every age range. Long-term neurobehavioral impacts, such as altered emotions and personalities, cognitive and mental deficits, and so on, are experienced by the majority of survivors. Our main objective is to understand the possible mechanism of the NLRP3 inflammasome in retinal neurons and enhance precision regarding reducing the burden of retinal neurodegeneration in TBI-induced AD. Both primary and secondary insults initiate the intricate pathophysiology of traumatic brain injury. Primary injuries are caused by mechanical force and occur right after the collision. Long-lasting and delayed secondary injuries follow. Studies demonstrating the continuous nature of research on the relationship between retinal neurons and TBI-induced Alzheimer's disease (AD) include neurodegeneration, retinal changes, and inflammatory response biomarkers. TBI can cause changes that resemble those seen in AD. This includes the accumulation of tau tangles and amyloid-beta plaques, which are also observed in the retina and imply a potential relationship between AD, traumatic brain injury, and retinal health. The linkage between TBI and AD, the effect of the innate immune system in post-TBI AD, the function of immunological moderators, the activation and assembly of inflammasomes in TBI, the pathophysiology of TBI, and the connection between TBI and inflammasome activity were the main topics of discussion in the following discussions. Of particular interest was the potential mechanism by which the NLRP3 inflammasome, in conjunction with SREBP2 and SCAP inflammasome, in retinal neurons in TBI-induced AD. The thinning of RNFL, poor lipid metabolism, and new developments such as drug delivery technologies, lipid metabolism modulation in retinal neurons, and drug-targeting lipid pathways and their mechanisms are then covered in this article.

Aortic arterial stiffness associates with carotid intima-media thickness and carotid plaques in younger middle-aged healthy people.

PURPOSE: Aortic stiffness, assessed as estimated aortic pulse wave velocity (aPWV), and carotid intima-media thickness (cIMT) are markers of vascular age, and carotid plaques are a marker of early atherosclerosis. In this cross-sectional study we aimed to investigate the association between aPWV, cIMT and plaques across different age groups and in women and men, in a middle-aged healthy population. MATERIALS AND METHODS: Participants in the 6.5-year follow-up of the VIPVIZA trial who were aged 47, 57 and 67 underwent an oscillometric measurement which estimates aPWV between 2020 and 2023. Carotid ultrasound examinations were also performed. Linear and ordinal regression models were used to investigate how aPWV associates with cIMT and with carotid plaques, for the overall study group and stratified for age groups and sex. RESULTS: A total of 1046 subjects were included in the analyses. Linear associations between aPWV and cIMT (ß = 0.018, 95% CI: 0.006-0.030, p = 0.003), and between aPWV and plaques (OR: 1.19, 95% CI: 1.03-1.38, p = 0.018), were seen in the 57-year-olds. In the 47-year-olds a significant association was seen between aPWV and plaques (OR: 2.98 95% CI: 1.44-6.14, p = 0.003). No significant associations were seen in the 67-year-olds. For women, a significant association between aPWV and cIMT (ß = 0.011, 95% CI: 0.004-0.017, p = 0.002) was shown. CONCLUSION: Estimated aPWV was positively associated with increasing cIMT and the presence of carotid plaques in younger middle-aged individuals, and with cIMT in women, suggesting that measurement of estimated aPWV may improve cardiovascular risk assessment in younger middle-aged individuals and women.Clinical Trial Registration date 8 May 2013: URL: www.clinicaltrials.gov. Unique identifier: NCT01849575.

What is the context? Vascular ageing is a process where the arteries become stiff, leading to impaired function and organ damage. Stiff arteries increase the risk of cardiovascular disease. Aortic pulse wave velocity is a measurement of arterial stiffness and a marker of vascular age. Carotid intima-media thickness and carotid plaque presence are other markers of vascular age and early atherosclerosis. There are limited data on the association between aortic pulse wave velocity, carotid intima-media thickness and carotid plaques.What is new? We measured estimated aortic pulse wave velocity using an oscillometric device and performed carotid ultrasound examinations for assessment of carotid intima-media thickness and carotid plaques in healthy middle-aged individuals across three different age groups. The association between aortic pulse wave velocity, carotid intima-media thickness and carotid plaques was examined in the different age groups and in women and men separately.What is the impact? Estimated aortic pulse wave velocity was associated with carotid intima-media thickness and carotid plaques in younger middle-aged individuals and with carotid intima-media thickness in women. Suggesting that for these groups ­ healthy younger middle-aged people, and especially women ­ measurement of estimated aortic pulse wave velocity could improve evaluation of cardiovascular risk.

Multifunctional Tasks and an Energy Crisis are Crucial Players in Determining the Vulnerability of the Entorhinal Cortex to Early Damage in Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating neurological disorder that affects synaptic transmission between neurons. Several theories and concepts have been postulated to explain its etiology and pathogenesis. The disease has no cure, and the drugs available to manage AD symptoms provide only modest benefits. It originates in the brain's entorhinal cortex (EC), with tau pathology that can proceed overt symptoms by decades and then spreads to other connected areas and networks to cause severe cognitive decline. Despite decades of research, the reason why the EC is the first region to be affected during AD pathophysiology remains unknown. The EC is well connected with surrounding areas to support the brain's structural and functional integrity, participating in navigation, working memory, memory consolidation, olfaction, and olfactory-auditory coordination. These actions require massive energy expenditure; thus, the EC is extremely vulnerable to severe hypometabolism and an energy crisis. Unfortunately, the crucial events/factors that make the EC vulnerable to pathological sequelae more than other brain regions have not been thoroughly explored. An in-depth analysis of available research on the role of the EC in AD could provide meaningful insights into the susceptibility of this region and its role in propagating AD. In this review article, we highlight how the functional complexities of the EC account for its vulnerability in AD.

Hypertension-Mediated Organ Damage in Relation to Severity of Chronic Low Back Pain in Hypertensive Patients.

INTRODUCTION: Chronic pain triggers a stress response, which results in increased blood pressure (BP). We investigated whether chronic low back pain (cLBP) in hypertensive patients is associated with an increased risk of hypertension-related organ damage. METHODS: We studied 85 consecutive hypertensive patients with a median age of 62 years (55-67), who suffered from cLBP, the severity of which was evaluated according to the Oswestry Disability Index (ODI). Patients underwent transthoracic echocardiography, arterial ultrasonography and vascular tonometry. We assessed carotid artery atherosclerotic plaques, along with carotid-femoral pulse wave velocity (cf-PWV) and left ventricular mass index (LVMI). RESULTS: An equal to or higher than median (16 points) ODI score in 48 subjects (56.5%) was associated with the presence of carotid artery plaques (p = 0.014). In multivariate analysis, after adjusting for covariates, the presence of carotid artery plaques remained independently associated with an ODI score equal to or higher than the median (OR, 3.71; 95% CI, 1.04-13.25; p = 0.044). None of the other analyzed parameters of hypertension-related organ damage demonstrated a significant relationship with the ODI score. CONCLUSIONS: We observed that more severe cLBP is associated with a higher prevalence of carotid artery atherosclerotic plaques among hypertensive patients.

Human Alzheimer's Disease ATN/ABC Staging Applied to Aging Rhesus Macaque Brains: Association With Cognition and MRI-Based Regional Gray Matter Volume.

The brain changes of Alzheimer's disease (AD) include Abeta (Aß) amyloid plaques ("A"), abnormally phosphorylated tau tangles ("T"), and neurodegeneration ("N"). These have been used to construct in vivo and postmortem diagnostic and staging classifications for evaluating the spectrum of AD in the "ATN" and "ABC" ("B" for Braak tau stage, "C" for Consortium to Establish a Registry for Alzheimer's Disease [CERAD] neuritic plaque density) systems. Another common AD feature involves cerebral amyloid angiopathy (CAA). We report the first experiment to examine relationships among cognition, brain distribution of amyloid plaques, CAA, tau/tangles, and magnetic resonance imaging (MRI)-determined volume changes (as a measure of "N") in the same group of behaviorally characterized nonhuman primates. Both ATN and ABC systems were applied to a group of 32 rhesus macaques aged between 7 and 33 years. When an immunohistochemical method for "T" and "B" was used, some monkeys were "triple positive" on ATN, with a maximum ABC status of A1B2C3. With silver or thioflavin S methods, however, all monkeys were classified as T-negative and B0, indicating the absence of mature neurofibrillary tangles (NFTs) and hence neuropathologically defined AD. Although monkeys at extremes of the ATN and ABC classifications, or with frequent CAA, had significantly lower scores on some cognitive tests, the lack of fully mature NFTs or dementia-consistent cognitive impairment indicates that fully developed AD may not occur in rhesus macaques. There were sex differences noted in the types of histopathology present, and only CAA was significantly related to gray matter volume.

Clean intermittent catheterization in multiple sclerosis patients: An adherence and long-term follow-up study.

INTRODUCTION: Clean Intermittent Catheterization (CIC) is considered as a gold standard of treatment for bladder emptying disorders. A large amount of literature on CIC for patients suffering from neurological disorders is available, but there is a lack of research specifically concerning multiple sclerosis (MS) patients. Our primary outcome was to determine the characteristics of our population (sex, EDSS and age when CIC was introduced). Our secondary outcomes were to determine adherence of CIC. METHOD: As part of a multicenter, observational, retro-prospective study, data was collected from neuro-urologist consultation reports, and extracted from bladder diaries between 01/01/2000 and 31/03/24. MS patients, over 18 years, with the indication of CIC were included. RESULTS: 195 patients (72.3% women) were included, with a mean age of 49 years old. The median of follow-up was 9 years. Median EDSS at the start of the study was 5.5. There was an adherence rate of 65.1%. Urinary leakage was present in 74.2% of patients prior to CIC and 31.6% following CIC. CONCLUSION: Catheterization is mainly offered to patients with an EDSS between 0 and 7. Rate of adhesion is encouraging, with most patients still continuing to use CIC by the end of follow-up. During the follow-up, we observed a reduced leakage rate but CIC alone can not explain this improvement. Following studies should include a list of constraints and reasons of halted CIC.

Recent advancement in understanding of Alzheimer's disease: Risk factors, subtypes, and drug targets and potential therapeutics.

Alzheimer's disease (AD) is a significant neocortical degenerative disorder characterized by the progressive loss of neurons and secondary alterations in white matter tracts. Understanding the risk factors and mechanisms underlying AD is crucial for developing effective treatments. The risk factors associated with AD encompass a wide range of variables, including gender differences, family history, and genetic predispositions. Additionally, environmental factors such as air pollution and lifestyle-related conditions like cardiovascular disease, gut pathogens, and liver pathology contribute substantially to the development and progression of AD and its subtypes. This review provides current update and deeper insights into the role of diverse risk factors, categorizing AD into its distinct subtypes and elucidating their specific pathophysiological mechanisms. Unlike previous studies that often focus on isolated aspects of AD, our review integrates these factors to offer a comprehensive understanding of the disease. Furthermore, the review explores a variety of drug targets linked to the neuropathology of different AD subtypes, highlighting the potential for targeted therapeutic interventions. We further discussed the novel therapeutic options and categorized them according to their targets. The roles of different drug targets were comprehensively studied, and the mechanism of action of their inhibitors was discussed in detail. By comprehensively covering the interplay of risk factors, subtype differentiation, and drug targets, this review provides a deeper understanding of AD and suggests directions for future research and therapeutic strategies.

Prevalence of ascending aortic atheromatous plaques and risk factors in Thai cardiac surgery patients: A prospective cohort study.

Cerebral embolism, a serious complication in cardiac surgery, is significantly impacted by atheromatous plaques in the ascending aorta and aortic arch. However, data on the prevalence of these plaques in Asian populations are sparse. This study aimed to evaluate the prevalence of atheromatous plaques in the ascending aorta among Thai cardiac surgery patients, thereby facilitating risk stratification and improving preoperative management. We conducted intraoperative epiaortic ultrasound examinations on 239 cardiac surgery patients. Clinically significant atheromatous plaques were defined as those exceeding 3.0 mm in thickness. The collected demographic and clinical data included sex, age, body weight, height, American Society of Anesthesiologists physical status classification, smoking status, alcohol consumption, and comorbidities. Atheromatous plaques were found in 33.5 % of the ascending aortas and 41.4 % of the aortic arches. The primary risk factors were advanced age (over 80 years; relative risk (RR) 1.444, 95 % confidence interval (CI) 1.113-1.874, P = 0.006) and carotid stenosis (RR 1.247, 95 % CI 1.04-1.495, P = 0.017). The prevalence of atheromatous plaques in Thai cardiac surgery patients was significant, with older age and carotid stenosis being major risk factors. Preoperative aortic imaging, such as computed tomography angiography or epiaortic ultrasound, should be applied to cardiac surgery candidates. In resource-limited settings, prioritizing patients of advanced age or those with carotid stenosis for imaging is advised.

Activation of the muscle-to-brain axis ameliorates neurocognitive deficits in an Alzheimer's disease mouse model via enhancing neurotrophic and synaptic signaling.

Skeletal muscle regulates central nervous system (CNS) function and health, activating the muscle-to-brain axis through the secretion of skeletal muscle-originating factors ("myokines") with neuroprotective properties. However, the precise mechanisms underlying these benefits in the context of Alzheimer's disease (AD) remain poorly understood. To investigate muscle-to-brain axis signaling in response to amyloid ß (Aß)-induced toxicity, we generated 5xFAD transgenic female mice with enhanced skeletal muscle function (5xFAD;cTFEB;HSACre) at prodromal (4-months old) and late (8-months old) symptomatic stages. Skeletal muscle TFEB overexpression reduced Aß plaque accumulation in the cortex and hippocampus at both ages and rescued behavioral neurocognitive deficits in 8-month-old 5xFAD mice. These changes were associated with transcriptional and protein remodeling of neurotrophic signaling and synaptic integrity, partially due to the CNS-targeting myokine prosaposin (PSAP). Our findings implicate the muscle-to-brain axis as a novel neuroprotective pathway against amyloid pathogenesis in AD.

Chronic Oral Inoculation of Porphyromonas gingivalis and Treponema denticola Induce Different Brain Pathologies in a Mouse Model of Alzheimer Disease.

Periodontitis is a chronic inflammatory disease driven by dysbiosis in subgingival microbial communities leading to increased abundance of a limited number of pathobionts, including Porphyromonas gingivalis and Treponema denticola. Oral health, particularly periodontitis, is a modifiable risk factor for Alzheimer disease (AD) pathogenesis, with components of both these bacteria identified in postmortem brains of persons with AD. Repeated oral inoculation of mice with P. gingivalis results in brain infiltration of bacterial products, increased inflammation, and induction of AD-like biomarkers. P. gingivalis displays synergistic virulence with T. denticola during periodontitis. The aim of the current study was to determine the ability of P. gingivalis and T. denticola, grown in physiologically relevant conditions, individually and in combination, to induce AD-like pathology following chronic oral inoculation of female mice over 12 weeks. P. gingivalis alone significantly increased all 7 brain pathologies examined: neuronal damage, activation of astrocytes and microglia, expression of inflammatory cytokines interleukin 1ß (IL-1ß) and interleukin 6 and production of amyloid-ß plaques and hyperphosphorylated tau, in the hippocampus, cortex and midbrain, compared to control mice. T. denticola alone significantly increased neuronal damage, activation of astrocytes and microglia, and expression of IL-1ß, in the hippocampus, cortex and midbrain, compared to control mice. Coinoculation of P. gingivalis with T. denticola significantly increased activation of astrocytes and microglia in the hippocampus, cortex and midbrain, and increased production of hyperphosphorylated tau and IL-1ß in the hippocampus only. The host brain response elicited by oral coinoculation was less than that elicited by each bacterium, suggesting coinoculation was less pathogenic.

Canine pigmented viral plaques associated with application of potent topical glucocorticoids.

A six-year-old atopic boxer presented with pigmented viral plaques on the interdigital spaces and pinnae following treatment with potent topical glucocorticoids. The lesions regressed after treatment was discontinued, and recurred each time a topical glucocorticoid was resumed. A Chipapillomavirus was amplified from lesional tissue.

Osteogenic-Like Microenvironment of Renal Interstitium Induced by Osteomodulin Contributes to Randall's Plaque Formation.

Calcium oxalate (CaOx) kidney stones are common and recurrent, lacking pharmacological prevention. Randall's plaques (RPs), calcium deposits in renal papillae, serve as niduses for some CaOx stones. This study explores the role of osteogenic-like cells in RP formation resembling ossification. CaP crystals deposit around renal tubules, interstitium, and blood vessels in RP tissues. Human renal interstitial fibroblasts (hRIFs) exhibit the highest osteogenic-like differentiation potential compared to chloride voltage-gated channel Ka positive tubular epithelial cells, aquaporin 2 positive collecting duct cells, and vascular endothelial cells, echoing the upregulated osteogenic markers primarily in hRIFs within RP tissues. Utilizing RNA-seq, osteomodulin (OMD) is found to be upregulated in hRIFs within RP tissues and hRIFs following osteogenic induction. Furthermore, OMD colocalizes with CaP crystals and calcium vesicles within RP tissues. OMD can enhance osteogenic-like differentiation of hRIFs in vitro and in vivo. Additionally, crystal deposits are attenuated in mice with Omd deletion in renal interstitial fibroblasts following CaOx nephrocalcinosis induction. Mechanically, a positive feedback loop of OMD/BMP2/BMPR1A/RUNX2/OMD drives hRIFs to adopt osteogenic-like fates, by which OMD induces osteogenic-like microenvironment of renal interstitium to participate in RP formation. We identify OMD upregulation as a pathological feature of RP, paving the way for preventing CaOx stones.

A cross-sectional study comparing the expression of DNA repair molecules in subjects with and without atherosclerotic plaques.

BACKGROUND: Atherosclerosis, serving as the primary pathological mechanism at the core of cardiovascular disease, is now widely acknowledged to be associated with DNA damage and repair, contributing to atherosclerotic plaque formation. Therefore, molecules involved in the DNA repair process may play an important role in the progression of atherosclerosis. Our research endeavors to explore the contributions of specific and interrelated molecules involved in DNA repair (APE1, BRCA1, ERCC2, miR-221-3p, miR-145-5p, and miR-155-5p) to the development of atherosclerotic plaque and their interactions with each other. METHODS & RESULTS: Gene expression study was conducted using the real-time polymerase chain reaction (qRT-PCR) method on samples from carotid artery atherosclerotic plaques and nonatherosclerotic internal mammary arteries obtained from 50 patients diagnosed with coronary artery disease and carotid artery disease. Additionally, 50 healthy controls were included for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Although no difference was observed in mRNA gene expressions, we noted a decrease in miR-155-5p gene expression (p = 0.003) and an increase in miR-221-3p gene expression (p = 0.015) in plaque samples, while miR-145-5p gene expression remained unchanged (p = 0.57). Regarding serum 8-OHdG levels, patients exhibited significantly higher levels (1111.82 ± 28.64) compared to controls (636.23 ± 24.23) (p < 0.0001). CONCLUSIONS: In our study demonstrating the role of miR-155-5p and miR-221-3p in atherosclerosis, we propose that these molecules are potential biomarkers and therapeutic targets for coronary artery diseases and carotid artery disease.

Relationship between triglyceride-glucose index and carotid artery plaques in ischemic stroke patients: Based on blood pressure status, sex, and age.

BACKGROUND: Numerous studies have shown that the triglyceride-glucose (TyG) index is a reliable substitute marker for insulin resistance. Nevertheless, its correlation with carotid artery plaques (CAPs) among patients with ischemic stroke (IS) remains to be elucidated. METHODS: 9248 IS patients hospitalized at the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine were grouped according to the quartiles of TyG index. Patients were further stratified by blood pressure status, sex, age and hypertension control status. Employing logistic regression to examine the connection between the TyG index and CAPs.Additionally, analyzing the receiver operating characteristic (ROC) curve to evaluate the predictive value of the TyG index for CAPs. RESULTS: Participants with an elevated TyG index had an increased prevalence of CAPs. The TyG index was positively correlated with CAPs (OR: 1.26, CI: 1.14-1.40, P<0.001). Compared with normal blood pressure and prehypertensive patients, the TyG index was markedly correlated with CAPs among hypertensive patients (OR: 1.29, 95% CI: 1.15-1.44, P<0.001). Females had a higher OR value than males(OR: 1.31, 95% CI: 1.11-1.54, P=0.001 versus OR: 1.24, 95% CI: 1.09-1.41, P=0.001). Older patients (>60 years) had a higher OR value than their middle-aged counterparts (≤60 years) (OR: 1.35; 95% CI: 1.16-1.58, P<0.001 versus OR: 1.20; 95% CI: 1.05-1.37, P=0.007). Patients with poorly-controlled hypertension had a higher OR value than patients with well-controlled hypertension(OR: 1.36; 95% CI: 1.14-1.63, P=0.001 versus OR: 1.24; 95% CI: 1.07-1.44, P=0.003). After adjusting for potential confounding factors, the area under the ROC curve (AUC) value in the overall population, sex-stratified group, hypertensive patients and hypertension control status-stratified group were all above 0.7 (P<0.01), demonstrating good forecasting capability. CONCLUSIONS: In IS patients, the TyG index was significantly associated with CAPs. Additionally, this correlation was more pronounced in hypertensive patients, females, older individuals and patients with poorly-controlled hypertension.

Integrative proteomics identifies a conserved Aß amyloid responsome, novel plaque proteins, and pathology modifiers in Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare AD brain proteome and network changes with the brain proteomes of amyloid ß (Aß)-depositing mice to identify conserved and divergent protein networks with the conserved networks identifying an Aß amyloid responsome. Proteins in the most conserved network (M42) accumulate in plaques, cerebrovascular amyloid (CAA), and/or dystrophic neuronal processes, and overexpression of two M42 proteins, midkine (Mdk) and pleiotrophin (PTN), increases the accumulation of Aß in plaques and CAA. M42 proteins bind amyloid fibrils in vitro, and MDK and PTN co-accumulate with cardiac transthyretin amyloid. M42 proteins appear intimately linked to amyloid deposition and can regulate amyloid deposition, suggesting that they are pathology modifiers and thus putative therapeutic targets. We posit that amyloid-scaffolded accumulation of numerous M42+ proteins is a central mechanism mediating downstream pathophysiology in AD.

Harmony of Wnt pathway in Alzheimer's: Navigating the multidimensional progression from preclinical to clinical stages.

The Wnt pathway stands out as a pivotal signal transduction pathway, operating through two distinct modes of signaling: the canonical/ß-catenin pathway and the non-canonical pathway. Among these, the canonical pathway assumes a paramount role in various physiological and pathological processes within the human body. Particularly in the brain, Wnt exhibits involvement in fundamental physiological events including neuronal differentiation/survival, axonogenesis, neural stem cell regulation, synaptic plasticity, and cell cycle modulation. Notably, scientific evidence underscores the critical role of the Wnt pathway in the pathogenesis of Alzheimer's disease (AD), correlating with its involvement in key pathological features such as tau tangles, Amyloid-ß plaques, synaptic dysfunction, oxidative stress, mitochondrial dysfunction, cognitive impairments, and disruption of the blood-brain barrier integrity. This review aims to comprehensively explore the involvement and significance of Wnt signaling in Alzheimer's. Furthermore, it delves into recent advancements in research on Wnt signaling, spanning from preclinical investigations to clinical trials.

Widespread purplish-red plaques with plasma cell infiltrate: A rare type of lichen planus.

Diseases in which cutaneous plasma cell infiltrates predominate are rare and usually of unknown etiology, including those that transition from benign to malignant, such as cutaneous plasmacytosis, multicentric Castleman disease, and extramedullary plasmacytoma. These diseases may present as purplish, reddish-brown cutaneous plaques or nodules. Here, we report an exceptional case of lichen planus (LP) in which the patient had classic histopathological features, but the infiltrating inflammatory cells were plasma cells with restricted light chain expression. The patient presented with severe rashes, including purplish-red plaques and nodules, erythema, and erosions in the palmoplantar area, verrucous hyperplasia of the oral mucosa, and anonychia of the toes. These findings suggest a possible role of plasma cells with restricted light chain expression in the LP. Clinicians should closely follow patients for changes in their rash, perform repeat biopsies if necessary, and regularly conduct multisystemic evaluations.

Correlation between the TyG-BMI index and carotid plaque characteristics in middle-aged and elderly patients with acute myocardial infarction.

OBJECTIVE: The aim of this study is to investigate the correlation between the triglyceride-glucose-body mass index (TyG-BMI) and the characteristics of various carotid plaques in middle-aged and elderly patients with acute myocardial infarction (AMI). METHODS: A retrospective study was conducted on 380 patients with AMI hospitalized in the Cardiology Department of Kaifeng Central Hospital. Based on carotid ultrasound results, patients were divided into the following two groups: the stable plaque group and the unstable plaque group. Additionally, a control group comprising 380 healthy individuals visiting the hospital's physical examination center during the same timeframe was established. Fasting venous blood samples were collected from all participants to measure blood glucose and triglyceride. The baseline TyG-BMI index was calculated using the formula Ln [fasting triglyceride (mg/dL)×fasting blood glucose (mg/dL)/2]×BMI. The correlation between different plaque groups and the TyG-BMI index was analyzed. RESULTS: The TyG-BMI index was significantly higher in the unstable plaque group compared to the stable plaque group, with values of 252.81±29.99 and 201.92±28.72, respectively (P = 0.034). Spearman's correlation analysis showed a positive correlation between the instability of carotid plaques and the TyG-BMI index in patients with AMI (r = 0.521, P = 0.003). Logistic regression analysis indicated that the TyG-BMI index was an important risk factor for unstable carotid plaques in patients with AMI (OR = 2.691, 95% CI: 1.169-4.123). CONCLUSION: The findings of this study suggest that an elevated TyG-BMI index significantly increases the risk of unstable carotid plaques in patients with AMI, making it an important risk factor for carotid plaque instability.