Current Alzheimer research最新文献

Oligodendrocytes (OLs) are the primary myelinating cells in the central nervous system (CNS), responsible for maintaining the rapid conduction of nerve signals and ensuring neuronal stability through metabolic and nutritional support. Recent studies have reported that OLs are also involved in the development and progression of Alzheimer's disease (AD), particularly in the production and clearance of amyloid-beta (Aβ), exhibiting complex and critical regulatory functions. While traditional research has predominantly focused on the roles of neurons and microglia in Aβ metabolism, recent evidence indicates that OLs engage in a complex bidirectional interaction with Aβ in AD. On the one hand, OLs can produce Aβ, frequently generating aggregated and highly toxic Aβ42, which contributes to plaque expansion and disease progression. On the other hand, neuronderived Aβ exerts a concentration-dependent dual effect on OLs. At high concentrations, it induces oxidative stress and cell apoptosis, while at low concentrations, it promotes their differentiation and myelin repair functions. Therefore, OLs serve as both a "source" and a "target" of Aβ production and response, making them a key factor in AD pathogenesis. This review discusses the interaction between OLs and Aβ in AD, aiming to provide new perspectives on targeting OLs for AD therapy. Given the dual role of OLs in Aβ metabolism, targeting OLs dysfunction and the regulatory mechanisms underlying Aβ production and clearance could provide novel therapeutic strategies for AD. Future research should investigate the roles of specific OL populations (including oligodendrocyte precursor cells (OPCs), pre-myelinating OLs, and mature OLs) in Aβ generation and metabolism, focusing on the signaling pathways involved. Additionally, the molecular mechanisms by which OLs regulate other glial cells, such as astrocytes and microglia, through intercellular signaling to facilitate Aβ clearance and maintain neuroglial homeostasis warrant further exploration.

Introduction/objective: Given the role of inflammation in the development of both Alzheimer's disease (AD) and periodontal disease, it is plausible that periodontal disease may influence the progression of AD. Complete blood count (CBC) parameters may also serve as predictive indicators for this condition. This study investigated the predictive value of CBC parameters on the progression of AD in patients with periodontal disease.

Methods: Data from a prospective cohort study (n=90) with 6-month follow-up was analyzed. AD was assessed based on the Clinical Dementia Rating Scale. Records of C-reactive Protein (CRP) levels and CBC parameters measured within the 6 months preceding the participation date were evaluated. Cognitive assessments at the initial and 6th-month follow-up were performed using the Standardized Mini-Mental Test (SMMT). All patients underwent clinical periodontal examination.

Results and discussion: The difference in SMMT score change (ΔSMMT) and platelet distribution width (PDW) value between groups with and without periodontitis was statistically notable (p<0.05). The presence of periodontitis was found to be significantly associated with age, ΔSMMT, and PDW values using the multivariate logistic regression model (p<0.05). Furthermore, having Stage II and Stage III AD, periodontitis, age factor, and mean platelet volume (MPV) value had a notable impact on ΔSMMT (p<0.05). These findings may indicate that systemic inflammation as reflected by complete blood count parameters (such as PDW and MPV) may play a predictive role in cognitive decline in Alzheimer's disease patients with periodontitis.

Conclusion: PDW and MPV levels may have a predictive significance in clarifying the association between periodontitis and AD progression.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss. The etiology of AD is complex and multifactorial, with contributions from genetic, lifestyle, and environmental factors. Recent advances in genetics, epigenetics, and animal models have shed light on the underlying mechanisms of brain aging and the development of AD, revealing potential targets for therapeutic intervention. In this comprehensive review, we examine the current understanding of the genetic, lifestyle, and epigenetic factors that shape the landscape of brain aging and AD. We discuss recent findings in the field of AD genetics, including the role of the APOE gene, and the potential of novel genome-wide association studies to identify new genetic risk factors. We also review the impact of lifestyle factors, such as diet, exercise, and social engagement, on brain aging and AD, and explore the role of epigenetic mechanisms, such as DNA methylation and histone modifications, in shaping AD risk.

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system characterized by complex pathological manifestations and an unclear pathogenesis. Lithium chloride (LiCl) exhibits certain neuroprotective effects. However, its performance and mechanisms in different types of AD models remain unclear.

Methods: The streptozotocin (STZ)-induced AD rat model was used to evaluate the ameliorating effects of LiCl. LiCl was administered orally for one month, and then evaluations were conducted in terms of nerve electrophysiology, behavioral science, and molecular biology.

Results: In this study, STZ was found to significantly affect the electrophysiological functions and behavioral performances of rats. However, LiCl was able to mitigate these effects. Specifically, it led to the restoration of electrophysiological functions, with long-term potentiation (LTP) being successfully induced. LiCl also demonstrated favorable therapeutic effects in rats, as confirmed by the nest-building tests, Y-maze, and Morris water maze. Further research revealed that LiCl promoted the phosphorylation of GSK-3β in the hippocampal region of rats.

Discussion: These findings indicated that LiCl demonstrated beneficial effects on AD-like pathological changes in STZ-induced AD rats, possibly by activating GSK-3β phosphorylation in the hippocampus, improving electrophysiological functions, and further restoring behavioral characteristics.

Conclusion: In conclusion, LiCl demonstrated therapeutic potential for AD by improving neurophysiological and behavioral deficits via hippocampal GSK-3β phosphorylation.

Background: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting the central nervous system (CNS), with its etiology still shrouded in uncertainty. The interplay of extracellular amyloid-β (Aβ) deposition, intracellular neurofibrillary tangles (NFTs) composed of tau protein, cholinergic neuronal impairment, and other pathogenic factors is implicated in the progression of AD.

Objective: The current study endeavors to delineate the proteomic landscape alterations in the hippocampus of an AD murine model, utilizing proteomic analysis to identify key physiological and pathological shifts induced by the disease. This endeavor aims to shed light on the underlying pathogenic mechanisms, which could facilitate early diagnosis and pave the way for novel therapeutic interventions for AD.

Methods: To dissect the proteomic perturbations induced by Aβ and Presenilin-1 (PS1) in the AD pathogenesis, we undertook a label-free quantitative (LFQ) proteomic analysis focusing on the hippocampal proteome of the APP/PS1 transgenic mouse model. Employing a multi-faceted approach that included differential protein functional enrichment, cluster analysis, and protein-protein interaction (PPI) network analysis, we conducted a comprehensive comparative proteomic study between APP/PS1 transgenic mice and their wild-type C57BL/6 counterparts.

Results: Mass spectrometry identified a total of 4817 proteins in the samples, with 2762 proteins being quantifiable. Comparative analysis revealed 396 proteins with differential expression between the APP/PS1 and control groups. Notably, 35 proteins exhibited consistent temporal regulation trends in the hippocampus, with concomitant alterations in biological pathways and PPI networks.

Conclusions: This study presents a comparative proteomic profile of transgenic (APP/PS1) and wild-type mice, highlighting the proteomic divergences. Furthermore, it charts the trajectory of proteomic changes in the AD mouse model across the developmental stages from 2 to 12 months, providing insights into the physiological and pathological implications of the disease-associated genetic mutations.

Alzheimer's disease (AD) is the frequent form of dementia in the world. Despite over 100 years of research into the causes of AD, including amyloid and tau protein, the research has stalled and has not led to any conclusions. Moreover, numerous projects aimed at finding a cure for AD have also failed to achieve a breakthrough. Thus, the failure of anti-amyloid and anti-tau protein therapy to treat AD significantly influenced the way we began to think about the etiology of the disease. This situation prompted a group of researchers to focus on ischemic brain episodes, which, like AD, mostly present alterations in the hippocampus. In this context, it has been proposed that cerebral ischemic incidents may play a major role in promoting amyloid and tau protein in neurodegeneration in AD. In this review, we summarized the experimental and clinical research conducted over several years on the role of ischemic brain episodes in the development of AD. Studies have shown changes typical of AD in the course of brain neurodegeneration post-ischemia, i.e., progressive brain and hippocampal atrophy, increased amyloid production, and modification of tau protein. In the post-ischemic brain, the diffuse and senile amyloid plaques and the development of neurofibrillary tangles characteristic of AD were revealed. The above data evidently showed that after brain ischemia, there are modifications in protein folding, leading to massive neuronal death and damage to the neuronal network, which triggers dementia with the AD phenotype.

Alzheimer's disease (AD) is the most common type of dementia among middle-aged and elderly individuals. Accelerating the prevention and treatment of AD has become an urgent problem. New technology including Computer-aided drug design (CADD) can effectively reduce the medication cost for patients with AD, reduce the cost of living, and improve the quality of life of patients, providing new ideas for treating AD. This paper reviews the pathogenesis of AD, the latest developments in CADD and other small-molecule docking technologies for drug discovery and development; the current research status of small-molecule compounds for AD at home and abroad from the perspective of drug action targets; the future of AD drug development.

Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, with a significant burden on global health. AD is characterized by a progressive cognitive decline and memory loss. Emerging research suggests a potential link between periodontitis, specifically the presence of oral bacteria such as Porphyromonas gingivalis (P. gingivalis), and AD progression. P. gingivalis produces an enzyme, Agmatine deiminase (AgD), which converts agmatine to N-carbamoyl putrescine (NCP), serving as a precursor to essential polyamines. Recent studies have confirmed the correlation between disruptions in polyamine metabolism and cognitive impairment.

Objective: This study aims to investigate the dysregulation of P. gingivalis Agmatine deiminase (PgAgD) in the context of AD.

Methods: Saliva samples were collected from a total of 54 individuals, including 27 AD patients and 27 healthy controls. The expression of the PgAgD gene was analyzed using quantitative Real-- Time PCR.

Results: The results showed a significant decrease in PgAgD gene expression in the saliva samples of AD patients compared to healthy controls. This downregulation was found in AD patients with advanced stages of periodontitis. Additionally, a correlation was observed between the decrease in PgAgD expression and the 30-item Mini-Mental State Examination (MMSE) score.

Conclusion: These findings suggest that measuring PgAgD expression in saliva could be a noninvasive tool for monitoring AD progression and aid in the early diagnosis of patients with periodontitis. Further research is needed to validate our results and explore the underlying mechanisms linking periodontitis, PgAgD expression, and AD pathophysiology.