Curr Alzheimer Res [JOURNAL]
Sun
200 papers
Lithium Chloride Improves Electrophysiological and Memory Deficits in Rats with Streptozotocin-Induced Alzheimer's Disease.
Xing Z, Jiang X, Yang W … +3 more , Wang Y, Zhang X, Zhao C
Curr Alzheimer Res · 2025 · PMID 40755110 · Publisher ↗
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 cert...
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.
Integration of Neuroimaging and Molecular Biomarkers in the Diagnosis of Alzheimer's Disease and Frontotemporal Dementia: The Promise of fMRI.
Poszwa J, Słowikowski B, Owecki W … +4 more , Szymanowicz O, Jagodzinski PP, Kozubski W, Dorszewska J
Curr Alzheimer Res · 2025 · PMID 40755109 · Publisher ↗
INTRODUCTION: Dementia is a set of acquired and progressive neuropsychiatric disorders. The most common types of dementia include Alzheimer's Disease (AD) and Frontotemporal Dementia (FTD). Early intravital diagnosis of...
INTRODUCTION: Dementia is a set of acquired and progressive neuropsychiatric disorders. The most common types of dementia include Alzheimer's Disease (AD) and Frontotemporal Dementia (FTD). Early intravital diagnosis of both types of dementia is difficult. Both molecular and neuroimaging markers are important for the diagnosis of different types of dementia. METHODS: This review employed freely accessible databases, including PubMed, Google Scholar, and ScienceDirect, using keywords such as molecular parameters, neuroimaging factors, dementia, FTD, Alzheimer's disease, and fMRI. RESULTS: Among the molecular markers of dementia, there are parameters common to its various types and enabling their differentiation. These parameters include both genetic and biochemical factors. Markers include genetic factors that help differentiate AD from FTD (e.g., . Simultaneously, there are important biochemical parameters differentiating AD (amyloid-beta (Aβ), neurofibrillary tangles) from FTD (TDP-43, FUS, and different forms of tau protein aggregates). Currently, there is growing interest in neuroimaging studies in the differential diagnosis of dementia. Positron Emission Tomography (PET) imaging enables the quantification and localization of Aβ deposits in the brain through the selective binding of the Pittsburgh Compound-B (PiB) ligand. This method has become the standard in AD diagnostics. In the context of magnetic resonance imaging studies, it is worth noting the search for structural differences between AD (mainly affecting the temporal lobe, including the hippocampus and entorhinal cortex, and the parietal lobe) and FTD (primarily involving the prefrontal cortex, anterior temporal lobes, and subcortical structures, as well as exhibiting an anteroposterior gradient of atrophy). However, the method of the future appears to be functional Magnetic Resonance Imaging (fMRI), especially since functional changes precede structural changes in the development of dementia. DISCUSSION: The review encompasses the basic diagnostic criteria for AD and FTD dementia, as well as molecular and neuroimaging parameters important for the intravital diagnosis of these dementias. It seems that the use of fMRI can contribute to both early diagnosis and early introduction of targeted treatment in developing dementia. Although it is not yet widely used clinically, its diagnostic value is increasingly recognized. CONCLUSION: The benefits of fMRI studies complementing molecular markers in the diagnosis of dementia were highlighted.
Mapping the Connection Between Circadian Rhythms, Metabolism, and Neurodegeneration: Exploring Therapeutic Strategies.
Bhaskar R, Narayanan KB, Singh KK … +1 more , Han SS
Curr Alzheimer Res · 2025 · PMID 40676783 · Publisher ↗
Circadian rhythms are crucial for essential physiological functions such as metabolism, sleep-wake cycles, hormone balance, and cognitive abilities, which are regulated by the central Suprachiasmatic Nucleus (SCN) and pe...
Circadian rhythms are crucial for essential physiological functions such as metabolism, sleep-wake cycles, hormone balance, and cognitive abilities, which are regulated by the central Suprachiasmatic Nucleus (SCN) and peripheral clocks. Disruptions to circadian rhythms, which may be caused by aging, lifestyle factors, and environmental influences, are linked to metabolic disorders and Neurodegenerative Diseases (NDs). This review examines the reciprocal relationship between circadian control and metabolism, highlighting the molecular processes that maintain circadian rhythms and how these processes change with age. Aging diminishes SCN efficiency and disrupts peripheral clock alignment, leading to impaired physiological functions, increased oxidative stress, and neuroinflammation, all of which contribute to the progression of NDs such as Alzheimer's (AD), Parkinson's disease (PD), Huntington's disease (HD), etc. Emerging therapeutic strategies aim to restore circadian function through interventions, including bright light therapy, melatonin supplementation, and pharmacological agents targeting clock gene regulators and neuropeptides. Furthermore, lifestyle modifications, such as Structured Physical Activity (SPA) and Time-Restricted Feeding (TRF), can enhance circadian health by synchronizing metabolic and hormonal rhythms. Future directions include chrono-pharmacology, gene editing, and Artificial Intelligence (AI)-driven personalized medicine, all of which emphasize the development of tailored circadian therapies. Advancing circadian research holds the potential to facilitate better health outcomes and improve quality of life, while also addressing the growing concerns of the aging population and NDs.
Effective Analysis of Alzheimer's Disease and Mechanisms of Methyl-4- Hydroxybenzoate using Network Toxicology, Molecular Docking, and Machine Learning Strategies.
Wen J, Hu J, Yang X … +2 more , Luo F, Zou G
Curr Alzheimer Res · 2025 · PMID 40671224 · Publisher ↗
INTRODUCTION: Nowadays, the large increase in environmental pollutants has led to the occurrence and development of an increasing number of diseases. Studies have shown that exposure to environmental pollutants, such as...
INTRODUCTION: Nowadays, the large increase in environmental pollutants has led to the occurrence and development of an increasing number of diseases. Studies have shown that exposure to environmental pollutants, such as methyl-4-hydroxybenzoate (MEP) may lead to Alzheimer's disease (AD). Therefore, the purpose of this study was to elucidate the complex effects and potential molecular mechanisms of environmental pollutants MEP on AD. METHODS: Through exhaustive exploration of databases, such as ChEMBL, STITCH, SwissTarget- Prediction, and Gene Expression Omnibus DataSets (GEO DataSets), we have identified a comprehensive list of 46 potential targets closely related to MEP and AD. After rigorous screening using the STRING platform and Cytoscape software, we narrowed the list to nine candidate targets and ultimately identified six hub targets using three proven machine learning methods (LASSO, RF, and SVM): CREBBP, BCL6, CXCR4, GRIN1, GOT2, and ITGA5. The "clusterProfiler" R package was used to conduct GO and KEGG enrichment analysis. At the same time, we also constructed disease prediction models for core genes. At last, six hub targets were executed molecular docking. RESULTS: We derived 46 key target genes related to MEP and AD and conducted gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. MEP might play a role in AD by affecting the pathways of neuroactive ligand-receptor interaction. Nine genes were screened as pivotal targets, followed by machine learning methods to identify six hub targets. Molecular docking analysis showed a good binding ability between MEP and CREBBP, BCL6, CXCR4, GRIN1, GOT2 and ITGA5. In addition, changes in the immune microenvironment revealed a significant impact of immune status on AD. DISCUSSIONS: This study revealed that MEP may induce AD through multiple mechanisms, such as oxidative stress, neurotoxicity, and immune regulation, and identified six core targets (CREBBP, BCL6, etc.) and found that they are related to changes in the immune microenvironment, such as T cells and B cells, providing new molecular targets for AD intervention. CONCLUSION: Overall, CREBBP, BCL6, CXCR4, GRIN1, GOT2, and ITGA5 have been identified as the crucial targets correlating with AD. Our findings provide a theoretical framework for understanding the complex molecular mechanisms underlying the effects of MEP on AD and provide insights for the development of prevention and treatment of AD caused by exposure to MEP.
Identification of MicroRNA Drug Targets for Alzheimer's and Diabetes Mellitus Using Network Medicine.
Castillo-Velazquez R, Castaneda-Delgado JE, Garcia-Hernandez MH … +6 more , Rivas-Santiago B, Ruiz-Hernandez S, Ortiz-Perez EL, Lopez-Alvarenga JC, Rivera G, Lara-Ramirez EE
Curr Alzheimer Res · 2025 · PMID 40662549 · Publisher ↗
INTRODUCTION: Type 2 diabetes mellitus (T2D) is a known risk factor for developing Alzheimer's disease (AD). Recent research shows that both diseases share complex and related pathophysiological processes. Network medici...
INTRODUCTION: Type 2 diabetes mellitus (T2D) is a known risk factor for developing Alzheimer's disease (AD). Recent research shows that both diseases share complex and related pathophysiological processes. Network medicine approaches can help to elucidate common dysregulated processes among different diseases, such as AD and T2D. Thus, the aim of this work was to determine differentially expressed genes (DEGs) in AD and T2D and to apply a network medicine approach to identify the microRNAs (miRNAs) involved in the AD-T2D association. METHODS: Gene expression microarray data sets consisting of 384 control samples and 399 samples belonging to AD and T2D disease were analyzed to obtain DEGs shared by both diseases; the miRNAs associated with these DEGs were predicted using a network medicine approach. Finally, potential small molecules targeting these potentially deregulated miRNAs were identified. RESULTS: AD and T2D shared a subset of 82 downregulated DEGs. These genes were significantly associated (p < 0.01) with the ontology terms of chemical synaptic deregulation. DEGs were associated with 12 miRNAs expressed in specific tissues for AD and T2D. Such miRNAs were also primarily associated with the ontology terms related to synaptic deregulation and cancer, and AKT signaling pathways. Steroid anti-inflammatory drugs, antineoplastics, and glucose metabolites were predicted to be potential regulators of the 12 shared miRNAs. DISCUSSION: The network medicine approach integrating DEGs and miRNAs enabled the identification of shared, potentially deregulated biological processes and pathways underlying the pathophysiology of AD and T2D. These common molecular mechanisms were also linked to drugs currently used in clinical practice, suggesting that this strategy may inform future drug repurposing efforts. Nonetheless, further in-depth biological validation is required to confirm these findings. CONCLUSION: Network medicine allowed identifying 12 miRNAs involved in the AD-T2D association, and these could be drug targets for the design of new treatments; however, the identified miRNAs need further experimental confirmation.
The Interaction between Oligodendrocytes and Aβ in Alzheimer's Disease.
Wang W, Huang X, Xu Z … +1 more , Yu C
Curr Alzheimer Res · 2025 · PMID 40626545 · Full text
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 nutrit...
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.
Comprehending Alzheimer's Disease: Molecular Mechanisms and Treatment Strategies.
Rathee S, Pandey V, Soni S … +2 more , Sen D, Jain SK
Curr Alzheimer Res · 2025 · PMID 40621760 · Publisher ↗
Alzheimer's disease (AD) is a complex neurodegenerative disorder and a growing global health challenge, driven by increasing life expectancy and an aging population. This review provides a comprehensive exploration of AD...
Alzheimer's disease (AD) is a complex neurodegenerative disorder and a growing global health challenge, driven by increasing life expectancy and an aging population. This review provides a comprehensive exploration of AD pathophysiology, integrating current hypotheses such as the amyloid cascade, tau protein pathology, cholinergic dysfunction, neuroinflammation, vascular contributions, and potential infection-related mechanisms. The multifactorial etiology of AD, encompassing genetic predispositions and environmental factors, underscores its intricate nature. This study delves into the diagnostic advancements, including the identification and utilization of biomarkers for early detection and disease monitoring. Therapeutic approaches are critically evaluated, highlighting anti-amyloid and anti-tau strategies, alongside emerging innovations in stem cell therapy and nanobiotechnology. A detailed examination of clinical trials offers insights into the achievements and setbacks of translating research into effective treatments. By synthesizing epidemiological trends, molecular mechanisms, and therapeutic developments, this review aims to advance our understanding of AD and foster collaborative efforts to develop transformative solutions. It emphasizes the urgency of addressing this multifaceted disease, presenting a nuanced perspective on its complexity while illuminating future directions for research and clinical practice.
History of Senile Dementia from the Antiquity to the Beginning of the Modern Age.
Raudino F
Curr Alzheimer Res · 2025 · PMID 40611424 · Publisher ↗
AIMS: This study aims, to trace the history of age-associated dementia from the earliest historical periods to the beginning of the modern age. BACKGROUND: Since the medical literature prior to the early 19th century is...
AIMS: This study aims, to trace the history of age-associated dementia from the earliest historical periods to the beginning of the modern age. BACKGROUND: Since the medical literature prior to the early 19th century is relatively scarce, the near absence of senile dementia has been hypothesized. OBJECTIVE: Verify the prevalence of senile dementia across different historical periods. METHODS: Beyond the medical literature, reviewed papers addressing legal and social aspects were examined to provide a comprehensive overview of the subject. RESULTS: While the medical literature on the subject is limited, there are a greater abundance of sources discussing social and legislative aspects. The scientific study of dementia had began only in the early 1800s. CONCLUSION: In ancient times, dementia was not particularly rare, but it was often overlooked, as it was considered an inevitable consequence of aging.
Alterations of , and Genes in the Frontal Cortex in an Ischemic Model of Alzheimer's Disease with Long-Term Survival.
Pluta R, Kocki J, Bogucka-Kocka A … +2 more , Bogucki J, Czuczwar SJ
Curr Alzheimer Res · 2025 · PMID 40611423 · Publisher ↗
INTRODUCTION: Currently, there is no information on changes in the , and genes in the frontal cortex after brain ischemia with animal survival for 2 years. Furthermore, it is not known whether the BNIP3, CASP3, and BECN...
INTRODUCTION: Currently, there is no information on changes in the , and genes in the frontal cortex after brain ischemia with animal survival for 2 years. Furthermore, it is not known whether the BNIP3, CASP3, and BECN1 genes possess any influence on neurons in the frontal cortex due to ischemia. AIMS: The goal of the investigation was to evaluate alterations in the behavior of , and genes in the frontal cortex following ischemia with survival of 2 years. MATERIALS AND METHODS: Gene expression was assessed using an RT-PCR protocol at 2-30 days and 6-24-months after ischemia. RESULTS: BECN1 gene expression after ischemic injury was lower than the control group during 7-30- days and 18 months, whereas overexpression was noted after 2 days, 6-, 12- and 24 months. In the case of BNIP3 gene expression, it was lower than the control group for 2-7 days and higher than the control throughout the remaining time after ischemia. Increased expression of the CASP3 gene was observed except on days 7-30 following ischemia when its expression was lower compared to control values. DISCUSSION: The data seem to indicate that the observed changes in gene expression may reflect the activation and inhibition of different mechanisms involved in the advancement of neurodegeneration after ischemia. CONCLUSION: Overexpression of BECN1gene is likely to be associated with the induction of neuroprotective phenomena, whereas overexpression of BNIP3 and CASP3 genes can cause harmful effects.
Serum Biomarkers of Vascular Dysfunction, Neuropsychiatric Symptoms, and Clinical Severity of Alzheimer's Disease: A Cross-sectional Study.
Luca A, Politis A, Luca M … +5 more , Ferri R, Grasso M, Drago F, Nicoletti A, Serretti A
Curr Alzheimer Res · 2025 · PMID 40574360 · Publisher ↗
INTRODUCTION: The aim of this study was to assess the relationship between serum biomarkers of vascular dysfunction and neuropsychological performance in Alzheimer's disease (AD) patients. MATERIALS AND METHODS: In this...
INTRODUCTION: The aim of this study was to assess the relationship between serum biomarkers of vascular dysfunction and neuropsychological performance in Alzheimer's disease (AD) patients. MATERIALS AND METHODS: In this cross-sectional observational study, outpatients with AD who were referred to the Neuropsychiatry Clinic of the Eginition Hospital in Athens from January 2006 to December 2006 were consecutively enrolled. All the participants underwent a neuropsychological assessment. The serum concentrations of Apolipoprotein A1 (ApoA1), Vascular Cell Adhesion Molecule 1 (VCAM- 1), Intercellular Adhesion Molecule 1 (ICAM-1), Lipoprotein-A (LpA), and C-Reactive Protein (CR-P) were determined. RESULTS: Fifty-six AD patients were enrolled. ApoA1 was correlated with Mini Mental State Examination (MMSE) and AD Cooperative Study-Activities of Daily Living (ADCS-ADL). Combined biomarkers were correlated with MMSE, Neuropsychiatry Inventory, Clinical Dementia Rating Scale, and ADCS-ADL. DISCUSSION: Our study highlights the association between serum biomarkers of vascular dysfunction- specifically ApoA1, VCAM-1, ICAM-1, LpA, and CRP-and the cognitive and behavioral features of Alzheimer's Disease. CONCLUSION: These findings suggest that assessing vascular biomarkers may offer valuable insights into the pathophysiological mechanisms underlying cognitive and behavioral decline in AD.
RESIGN: Alzheimer's Disease Detection Using Hybrid Deep Learning based Res-Inception Seg Network.
Kannan A, Subramanian KSR, Suresh S
Curr Alzheimer Res · 2025 · PMID 40539353 · Publisher ↗
INTRODUCTION: Alzheimer's disease (AD) is a leading cause of death, making early detection critical to improve survival rates. Conventional manual techniques struggle with early diagnosis due to the brain's complex struc...
INTRODUCTION: Alzheimer's disease (AD) is a leading cause of death, making early detection critical to improve survival rates. Conventional manual techniques struggle with early diagnosis due to the brain's complex structure, necessitating the use of dependable deep learning (DL) methods. This research proposes a novel RESIGN model is a combination of Res-InceptionSeg for detecting AD utilizing MRI images. METHODS: The input MRI images were pre-processed using a Non-Local Means (NLM) filter to reduce noise artifacts. A ResNet-LSTM model was used for feature extraction, targeting White Matter (WM), Grey Matter (GM), and Cerebrospinal Fluid (CSF). The extracted features were concatenated and classified into Normal, MCI, and AD categories using an Inception V3-based classifier. Additionally, SegNet was employed for abnormal brain region segmentation. RESULTS: The RESIGN model achieved an accuracy of 99.46%, specificity of 98.68%, precision of 95.63%, recall of 97.10%, and an F1 score of 95.42%. It outperformed ResNet, AlexNet, Dense- Net, and LSTM by 7.87%, 5.65%, 3.92%, and 1.53%, respectively, and further improved accuracy by 25.69%, 5.29%, 2.03%, and 1.71% over ResNet18, CLSTM, VGG19, and CNN, respectively. DISCUSSION: The integration of spatial-temporal feature extraction, hybrid classification, and deep segmentation makes RESIGN highly reliable in detecting AD. A 5-fold cross-validation proved its robustness, and its performance exceeded that of existing models on the ADNI dataset. However, there are potential limitations related to dataset bias and limited generalizability due to uniform imaging conditions. CONCLUSION: The proposed RESIGN model demonstrates significant improvement in early AD detection through robust feature extraction and classification by offering a reliable tool for clinical diagnosis.
Efficacy of Sodium Valproate in Behavioral and Psychological Symptoms of Dementia: A Retrospective Observational Study from PUMCH Dementia Cohort.
Qiu Y, Shang L, Wang T … +8 more , Jiang Y, Bao J, Wang W, Li B, Huang Y, Dong L, Mao C, Gao J
Curr Alzheimer Res · 2025 · PMID 40530730 · Publisher ↗
INTRODUCTION: Behavioral and Psychological Symptoms of Dementia (BPSD) pose significant challenges for individuals with dementia and their caregivers. Agitation symptoms, in particular, present a complex management dilem...
INTRODUCTION: Behavioral and Psychological Symptoms of Dementia (BPSD) pose significant challenges for individuals with dementia and their caregivers. Agitation symptoms, in particular, present a complex management dilemma as there is a lack of consensus regarding pharmacotherapy, specifically with respect to the controversial use of valproate formulations. This study aims to assess the effectiveness of valproate treatment in addressing BPSD, with a specific focus on managing agitation symptoms in individuals with dementia. METHODS: A retrospective analysis was conducted at Peking Union Medical College Hospital (PUMCH) on patients diagnosed with BPSD who received valproate formulations between 2013 and 2023. Patients were classified into 'effective,' 'ineffective,' and 'unknown' groups based on their response to valproate treatment, and the distribution of BPSD symptoms between the effective and ineffective groups was compared. RESULTS: Among the 116 patients studied, 62.1% exhibited effective responses, 12.1% showed ineffectiveness, and 25.9% had uncertain outcomes with valproate therapy. While the effective group displayed a higher prevalence of agitation symptoms and other behaviors like wandering, restricted and repetitive behaviors, and sleep disturbances compared to the ineffective group, these differences did not reach statistical significance (p = 0.156, 1.000, 0.899, 0.283). Patients in the ineffective group were more likely to experience aggression with comorbid psychotic symptoms compared to those in the effective group (p = 0.023). DISCUSSION: Valproate may benefit agitation-predominant BPSD without psychosis. Discrepancies in prior findings may stem from differing dosing strategies. Its limited efficacy in psychosis-related aggression underscores the need for careful clinical evaluation. CONCLUSION: The findings suggest that tailored valproate treatment at low doses may be beneficial in managing agitation without psychosis in Asian BPSD patients. Further validation through randomized controlled trials is essential to substantiate these observations.
Association of Brain and Ventricular Boundary Shift Integral Measurements with CSF Biomarkers: A Case-Control Study.
Hosseini SF, Akbarabadi P, Noorani F … +7 more , Kazemi D, Sadeghsalehi H, Fattahpour M, Sheybani-Arani MH, Noroozi M, Kazemi A, Alzheimer's Disease Neuroimaging Initiative
Curr Alzheimer Res · 2025 · PMID 40491369 · Publisher ↗
AIMS: This study seeks to examine the relationship between cerebrospinal fluid (CSF) biomarkers (Aβ1-42, Phospho-Tau181p, Total-Tau) and brain volumetric changes measured by Brain Shift Integral (BSI) in Alzheimer's dise...
AIMS: This study seeks to examine the relationship between cerebrospinal fluid (CSF) biomarkers (Aβ1-42, Phospho-Tau181p, Total-Tau) and brain volumetric changes measured by Brain Shift Integral (BSI) in Alzheimer's disease (AD) spectrum. We explore the potential of BSI as a complementary, non-invasive tool for early diagnosis and progression monitoring of AD. BACKGROUND: AD is a neurodegenerative disorder marked by amyloid plaques and tau tangles, leading to cognitive decline. CSF biomarkers are key indicators of AD pathology, but their integration with imaging metrics like BSI could enhance early diagnosis. BSI quantifies brain volume changes via MRI, offering valuable insights into neurodegeneration across the AD spectrum. OBJECTIVES: The current study explores the use of BSI and CSF biomarkers for the early detection of Alzheimer's disease. METHODS: This study utilized data from the ADNI database, including CSF biomarkers (Aβ1-42, t-tau, ptau181) and BSI measurements from baseline and month 24 visits. Spearman correlations were performed to assess associations between biomarkers and brain volumetric changes. Linear regression models were used to examine the predictive value of biomarkers on BSI, controlling for potential confounders. RESULTS: A total of 239 participants were included in the study, comprising 94 cognitively normal (CN) individuals, 104 with mild cognitive impairment (MCI), and 41 with AD. Significant negative correlations were observed between Aβ1-42 and both BBSI and VBSI in MCI at baseline (p=0.013) and 24 months (p=0.018), as well as between Aβ1-42 and VBSI in CN at baseline (p=0.039) and 24 months (p=0.033). In MCI, p-tau181 was positively correlated with BBSI (p=0.013) and VBSI (p=0.030) at baseline and with BBSI at 24 months (p=0.013). Linear regression analysis confirmed that Aβ1-42 and p-tau181 significantly predicted BSI measures in MCI (R=0.141-0.173, p<0.05), while Aβ1-42 was a significant predictor of VBSI in CN (R2=0.156-0.166, p<0.01). No significant associations were found in AD. DISCUSSION: This study underscores the role of CSF biomarkers-particularly Aβ1-42 and p-tau181-in detecting early brain atrophy across the Alzheimer's disease spectrum, with limited utility in advanced stages. The findings highlight the importance of early intervention and support the integration of CSF biomarkers and BSI as diagnostic tools for monitoring disease progression and staging. CONCLUSION: The application of the BSI is pivotal for monitoring brain volume alterations and their association with CSF biomarkers.
Advance Nanotechnology-Based Drug Delivery Systems for Alzheimer's Disease: Advancements and Future Perspectives.
Singh K, Gupta JK, Lakhchora G … +5 more , Jain D, Bhatt A, Sharma MC, Chaitanya MVNL, Tabish M
Curr Alzheimer Res · 2025 · PMID 40491368 · Publisher ↗
Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, significantly impacting the quality of life for affected individuals. This manuscript explores vari...
Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, significantly impacting the quality of life for affected individuals. This manuscript explores various innovative therapeutic strategies aimed at enhancing drug delivery to the brain, particularly through the use of nanotechnology. This paper discussed the application of Solid Lipid Nanoparticles (SLNs), dendrimers, and Polymeric Nanoparticles (PNPs) in targeting the Central Nervous System (CNS) to improve bioavailability and therapeutic efficacy. The findings indicate that these advanced delivery systems can enhance brain penetration, reduce Amyloid-Beta (Aβ) deposition, and improve cognitive functions in animal models of AD. Furthermore, the review highlights the challenges associated with these technologies, including limited scalability and potential toxicity, while suggesting future directions for research and development in the field of AD treatment.
Proposed Therapeutic Strategy to Combat Alzheimer's Disease by Targeting Beta and Gamma Secretases.
Kumar D, Anand P, Singh SK
Curr Alzheimer Res · 2025 · PMID 40491367 · Publisher ↗
Alzheimer's disease (AD) is a degenerative neurological disease characterized by a loss of memory and cognitive ability. One of the main factors influencing the development of AD is the accumulation of amyloid β (Aβ) pla...
Alzheimer's disease (AD) is a degenerative neurological disease characterized by a loss of memory and cognitive ability. One of the main factors influencing the development of AD is the accumulation of amyloid β (Aβ) plaque in the brain. The sequential production of Aβ is mediated by two enzymes: gamma-secretase and β-secretase (BACE1). The goal of beta-secretase inhibitors is to prevent the initial cleavage of amyloid precursor protein (APP), which reduces the production of (Aβ) peptides by limiting the substrate available for gamma-secretase. Simultaneously, gamma-secretase modulators are engineered to specifically modify enzyme performance, reducing the synthesis of the harmful Aβ42 isoform while maintaining vital physiological processes. Targeting both secretases reduces amyloidogenic processing synergistically. Selective inhibitors, which have been recently developed, have also shown good clinical development. They can reduce Aβ levels effectively with minimal side effects. The therapeutic strategy also underlines the importance of early therapy intervention in the preclinical AD phase for an optimum effect. Although there are some problems in the optimization of drug delivery and the alleviation of side effects, targeting beta and gamma secretases remains a promising direction. However, all these strategies still need more research and clinical testing to improve existing treatments and develop new, efficient Alzheimer's disease therapies. This review seeks to examine the therapeutic promise of β- and γ-secretase inhibition in Alzheimer's disease and review recent progress, challenges, and new dual-inhibition approaches.
Assessment of the Inhibition of AChE and BChE by Essential Oil and Carline Oxide: Neuroprotective Effects and In Vivo Toxicity Assessment for the Management of Alzheimer's Disease.
Keniche A, Kalache C, Dib MEA … +1 more , El Ouar I
Curr Alzheimer Res · 2025 · PMID 40491366 · Publisher ↗
BACKGROUND: Alzheimer's disease is associated with dysfunction of the cholinergic system, making the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) a promising therapeutic approach. OBJECTIVE:...
BACKGROUND: Alzheimer's disease is associated with dysfunction of the cholinergic system, making the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) a promising therapeutic approach. OBJECTIVE: This study aimed to evaluate the neuroprotective effects and toxicity of essential oil (EO) and carlina oxide from Carthamus caeruleus in mice, assessing their potential for Alzheimer's disease treatment. METHODS: The chemical composition of the essential oil extracted from the roots of Carthamus caeruleus was analyzed using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The main component, carlina oxide, was isolated via column chromatography. The inhibitory activities of AChE and BChE were evaluated in vitro for both the essential oil and carlina oxide. Additionally, in vivo, toxicity was assessed in laboratory mice. RESULTS: Chemical analysis identified carlina oxide (81.6%) as the major constituent, along with minor compounds such as 13-methoxycarlin oxide and hexadecanoic acid. Both the essential oil and its main component, carlina oxide, exhibited significant inhibitory activity against AChE and BChE, enzymes associated with Alzheimer's disease. The essential oil demonstrated promising IC values, with stronger anti-BChE activity compared to the reference drug, galantamine. Toxicity tests in mice revealed no adverse effects at lower doses (0.2-0.5 g/kg). However, higher doses (1.0-2.0 g/kg) resulted in mild to significant toxicity, including weight loss and mortality. DISCUSSION: The essential oil and carlina oxide demonstrated potent BChE inhibition, particularly relevant in advanced Alzheimer's disease. While effective at low doses, signs of toxicity were observed at higher concentrations, highlighting the importance of dose optimization. These findings suggest that C. caeruleus may serve as a natural source of cholinesterase inhibitors, pending further studies and clinical validation. CONCLUSION: Carthamus caeruleus essential oil and carlina oxide show promising inhibitory effects on AChE and BChE, suggesting their potential as neuroprotective agents. However, their toxicity at higher doses highlights the need for cautious use and further investigation.
Exploring the Neuroprotective Potential of Polyphenolic Compounds in Mitigating Quinolinic Acid-Induced Neurotoxicity in Alzheimer's Disease.
Gandhi P, Panchal S
Curr Alzheimer Res · 2025 · PMID 40491365 · Publisher ↗
BACKGROUND: Quinolinic Acid (QA), a neurotoxic metabolite in the kynurenine pathway, contributes to neuronal damage, oxidative stress, and neuroinflammation, playing a key role in Alzheimer's Disease (AD) pathogenesis. T...
BACKGROUND: Quinolinic Acid (QA), a neurotoxic metabolite in the kynurenine pathway, contributes to neuronal damage, oxidative stress, and neuroinflammation, playing a key role in Alzheimer's Disease (AD) pathogenesis. This study investigates the neuroprotective potential of polyphenolic compounds, particularly lycopene and a Curcumin-Zinc (Cur-Zn) complex, using in- -silico and in-vitro approaches targeting the kynurenine pathway. METHODOLOGY: This study evaluated the neuroprotective potential of lycopene and Cur-Zn complex using and approaches. Molecular docking was performed to assess their binding affinities with the kynurenine pathway enzymes, and in-vitro neuroprotection assays on N2a cells measured their efficacy against QA-induced oxidative stress. RESULTS: Docking analysis revealed strong binding affinities of Cur-Zn and lycopene to IDO1 and KMO, with fitness scores of 143.11 and 126.41, respectively, indicating their potential as enzyme- specific inhibitors. Lycopene exhibited the most potent neuroprotective effect (IC50 = 0.63 μM), followed by Cur-Zn (1.59 μM). Both compounds significantly reduced QA-induced ROS levels, as confirmed by DCFDA fluorescence imaging. Additionally, they upregulated KAT and QPRT enzymes, promoting neuroprotective metabolite production. DISCUSSION: Lycopene and Cur-Zn effectively modulate key kynurenine pathway enzymes while mitigating oxidative stress, supporting their potential as neuroprotective agents. Although bisabolol and bromelain exhibited some efficacy, their effects were comparatively lower. CONCLUSION: Lycopene and Cur-Zn are promising candidates for AD therapy, demonstrating not only anti-oxidant activity but also a capacity to minimise the neurotoxic effects of QA, offering a dual mechanism of action. Further, studies are needed to validate their therapeutic potential in neurodegenerative diseases.
Association between Obesity and Cognitive Function in Chinese Older Adults: The Mediating Effects of Sleep Quality and Blood Pressure.
Li S, Yong C, Xiong Y … +8 more , Li N, Yue Z, Liu W, Liu Q, Li X, Ye Q, Wang Y, Zhou J
Curr Alzheimer Res · 2025 · PMID 40454493 · Publisher ↗
INTRODUCTION: The mechanisms underlying the relationship between obesity and cognitive function remain unclear, particularly among older adults, where reliable evidence is limited. This study aimed to explore whether the...
INTRODUCTION: The mechanisms underlying the relationship between obesity and cognitive function remain unclear, particularly among older adults, where reliable evidence is limited. This study aimed to explore whether the relationship between obesity and cognitive function is mediated by sleep quality and blood pressure (BP) in older Chinese adults. METHODS: We conducted an observational study using data from a cluster randomized controlled trial (RCT) with 5 follow-up periods involving older adults in rural China. The trial took place in Sichuan, China, from May 2021 to May 2023. Telephone Interview for Cognitive Status (TICS- 10) was used to assess the participants' cognitive function. Additionally, linear mixed-effects models and mediation analyses were performed. RESULTS: The mean age of participants was 70.89, and 225 out of 506 participants were males. Weight, waist circumference (WC), and hip circumference (HC) were positively associated with cognitive function, while compared to normal/underweight participants, participants with overweight had a significant association with cognitive function. Sleep quality mediated the association between weight and cognitive function (β = 0.01, (95% CI: 0.00 to 0.01), P < 0.001), accounting for a mediating effect proportion of 4.04% (95% CI: 2.19% to 8.00%). Diastolic blood pressure (DBP) mediated the association between overweight (β = 0.02, (95% CI: 0.00 to 0.05), P < 0.001), HC (β = 0.01, (95% CI: 0.00 to 0.01), P = 0.02), and WC (β = 0.01, (95% CI: 0.00, 0.01), P <0.001) and cognitive function, explaining approximately 4.46% (95% CI: 0.41% to 12.00%), 7.16% (95% CI: 0.36%, 17.00%), and 9.60% (95% CI: 1.11%, 25.00%) mediating proportion of the total effect, respectively. DISCUSSION: Our study highlights the potential mediating roles of sleep quality and DBP in the relationship between obesity and cognitive function. The findings contribute to understanding the obesity-cognition link in older adults, particularly in rural settings. However, limitations, such as self-reported sleep measures and unmeasured confounders, warrant caution. Further research is needed to clarify the underlying mechanisms and inform targeted interventions. CONCLUSION: Our study demonstrates a significant positive association between weight, body mass index (BMI), HC, and WC and cognitive function in older adults. These findings suggest that maintaining a moderately high level of overweight may be protective against cognitive decline in this population. Additionally, the study also provides insights into optimizing cognitive function through factors, such as sleep and BP management.
Therapeutic Advances in Alzheimer’s Disease: Integrating Natural, Semi-Synthetic, and Synthetic Drug Strategies.
Chauhan BS, Singh YP, Poeggeler B … +1 more , Singh SK
Curr Alzheimer Res · 2025 · PMID 40454492 · Publisher ↗
Alzheimer's disease (AD) is a neurodegenerative disorder associated with age, marked by progressive memory loss linked to the decline of cholinergic neurons, accumulation of amyloid plaques, and the presence of Neurofibr...
Alzheimer's disease (AD) is a neurodegenerative disorder associated with age, marked by progressive memory loss linked to the decline of cholinergic neurons, accumulation of amyloid plaques, and the presence of Neurofibrillary Tangles (NFTs). Neuropil threads in the brain contribute to amyloidosis and dementia. Despite extensive research, AD's etiology remains unclear, and currently, no promising therapy exists. This review examines the role of natural, semi-synthetic, and synthetic drugs in AD treatment. Natural drugs demonstrate safety and efficacy with minimal adverse effects, while most agents, whether natural or synthetic, target multiple steps or directly counteract amyloidogenesis, tau protein pathology, oxidative stress, NMDA receptor activity, inflammation, acetylcholine (AChE) function, or α, β, γ secretase activity. In pursuit of improved treatment outcomes, we explore the effectiveness and challenges of various therapeutic interventions. Our hypothesis underscores the importance of an integrated approach combining these drug types for tailored symptom relief, suggesting combined therapies may offer greater therapeutic benefits compared to single-drug approaches. The drugs discussed show potential in regulating AD, thereby presenting viable options for its management. However, to obtain more favorable results, additional studies are needed by combining these drugs.
Anthocyanidins Intake is Associated with Alzheimer's Disease Risk in Americans over 60 Years of Age: Data from NHANES 2007-2008, 2009-2010, and 2017-2018.
Chen Y, Zhao J, Li C … +2 more , Yao Y, Shang Y
Curr Alzheimer Res · 2025 May · PMID 40454491 · Publisher ↗
OBJECTIVE: At present, there is limited research on the association between dietary intake of anthocyanidins and Alzheimer's disease (AD). More epidemiological studies are needed to better understand this relationship. M...
OBJECTIVE: At present, there is limited research on the association between dietary intake of anthocyanidins and Alzheimer's disease (AD). More epidemiological studies are needed to better understand this relationship. METHODS: We explored the relationship between dietary Anthocyanidins intake and AD among 3806 American adults in the National Health and Nutrition Examination Survey (NHANES) and the United States Department of Agriculture's Food and Nutrient Database for Dietary Studies (FNDDS) from 2007 to 2010, and 2017 to 2018. We use weighted logistic regression model, restricted cubic spline (RCS) and weighted quantile sum (WQS) regression analysis to analyze the relationship between anthocyanidins monomer and AD. RESULTS: The weighted logistic regression model showed that the total intake of anthocyanidins was the fourth (OR:0.979; 95% CI: 0.966-0.992) quantile (relative to the lowest quantile) is related to the reduction of AD risk. RCS analysis showed that the total intake of anthocyanidins was negatively linearly correlated with AD (nonlinear P value was 0.002). The WQS regression analysis shows that cyanidin and malvidin are the main contributors to the comprehensive effects of six anthocyanidins. CONCLUSION: Our results show that a higher dietary intake of anthocyanidins is associated with a lower risk of AD.
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