Curr Alzheimer Res [JOURNAL]
Sun
200 papers
Auditory Hallucinations as the First Symptom of Alzheimer´s Disease - A Case Report.
Husing T, Quante A
Curr Alzheimer Res · 2025 · PMID 41126412 · Publisher ↗
INTRODUCTION: Neuropsychiatric symptoms frequently occur in patients with Alzheimer´s disease (AD); apathy, depression, delusions, optical hallucinations, anxiety, and agitation often appear as first symptoms of AD, whil...
INTRODUCTION: Neuropsychiatric symptoms frequently occur in patients with Alzheimer´s disease (AD); apathy, depression, delusions, optical hallucinations, anxiety, and agitation often appear as first symptoms of AD, while auditory hallucinations have never been described as the first symptom. In this case report, we describe a case of a woman who had auditory hallucinations as the first symptom of AD. CASE PRESENTATION: An 85-year-old woman was admitted to our hospital suffering from imperative auditory hallucinations without subjective and minimal objective memory complaints. Further diagnostics with an MRI scan, neuropsychological tests, and an analysis of cerebral spinal fluid were accomplished. AD was confirmed during the hospital stay, suggesting auditory hallucinations as the first symptom of AD. She was temporarily treated with risperidone, which improved the hallucinations. CONCLUSION: Auditory hallucinations in older age could be the first symptom of AD and even occur before cognitive decline.
The Comparison Between Dietary Vitamin A Deficiency and the CRP Level in Alzheimer's Disease in Patients with Type 2 Diabetes: A Case-Control Study.
Saeed RB, Alkharouby RA, Niaz LA … +7 more , Maddah RA, Ismail WM, Tonkal LA, Sultan L, Jastaniah N, Khan MA, Alhalwani AY
Curr Alzheimer Res · 2025 · PMID 41121477 · Publisher ↗
BACKGROUND: Type 2 Diabetes Mellitus (T2DM) patients are 50-60% more likely to develop Alzheimer's Disease (AD). T2DM has many risk factors, including inflammation. Previous studies suggest that CRP was higher in diabeti...
BACKGROUND: Type 2 Diabetes Mellitus (T2DM) patients are 50-60% more likely to develop Alzheimer's Disease (AD). T2DM has many risk factors, including inflammation. Previous studies suggest that CRP was higher in diabetic patients, indicating that it may play a role in diabetogenesis and insulin resistance. Many diseases are prevalent in older age, including T2DM and AD. Moreover, multiple studies suggested a possible association between vitamin A levels, AD, and T2DM. However, the role of Vitamin A in Alzheimer's patients with T2DM has not yet been fully investigated. Therefore, this study aims to measure the association between dietary vitamin A deficiency and AD patients with T2DM in King Abdulaziz Medical City, Jeddah, Western Region, Saudi Arabia, to help expand the preexisting knowledge of the diagnostic risk factors of both the diseases and to determine the significance of vitamin A as a nutritional factor in their management and prevention. METHODS: This case-control study investigates the prevalence of vitamin A deficiency (VAD) among Alzheimer's disease (AD) patients with and without type 2 diabetes mellitus (T2DM). Participants included 103 AD patients aged 40 and older from the National Guard Hospital in Saudi Arabia, recruited between 2016 and 2022. Data collection occurred in two phases: first, through a review of medical records to gather demographic and health history information, including retrospective blood tests for systemic C-reactive protein (CRP) levels and comorbidities; second, using the HKI Food Frequency Questionnaire (FFQ) to assess dietary intake of vitamin A-rich foods over the past week, with caregiver interviews facilitating this process. Each subject was also prospectively interviewed to assess the presence of VAD events. The study aims to elucidate the relationship between dietary habits and VAD prevalence in AD patients, contributing to the understanding of nutritional impacts on cognitive health in this population. RESULTS: This study examined demographic and clinical characteristics of the Alzheimer's group, with 70.1% having both Alzheimer's with T2DM and 29.9% having Alzheimer's alone. Significant differences in age were found (p-value = 0.03), but gender distribution was similar (p-value = 0.45). Most caregivers were sons, and 81.43% of patients received oral feeding. Comorbidities included hypertension (94.90%) and dyslipidemia (63.4%), with significant differences (p-value < 0.001). Correlation analyses showed weak negative correlations between CRP and vitamin A concentrations in both groups (Alzheimer with T2DM: p-value = 0.713, rho = -0.064; AD only: p-value = 0.223, rho = -0.121). Age and vitamin A levels also exhibited weak correlations: Alzheimer's with 2DM (p-value = 0.727, rho = 0.053) and Alzheimer's only (p-value = 0.223, rho = -0.253), neither of them was statistically significant. Symptoms of vitamin A deficiency were noted in Alzheimer's patients with T2DM, with no significant differences between groups. Dietary intake was lower for vitamin B complex, vitamin D, and multivitamins in AD patients with T2DM. CONCLUSION: The findings highlight the need for further investigation into the factors influencing vitamin A metabolism in these populations. Additionally, the prevalence of vitamin A deficiency symptoms and low dietary intake of essential nutrients among patients with Alzheimer's with T2DM suggests critical areas for nutritional intervention. Addressing these deficits may improve patient outcomes and enhance overall care strategies for individuals living with Alzheimer's disease.
An Multi-Omics Investigation of Alzheimer's Disease Linking Gene Dysregulation, Mutations, and Protein Networks to Core Pathologies.
Abd-Alkareem MA, Jasim RH, Mashaan AO … +1 more , Suleiman AA
Curr Alzheimer Res · 2025 · PMID 41116277 · Publisher ↗
INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by synaptic dysfunction and the accumulation of amyloid plaques. The molecular mechanisms linking gene dysregulation, pathogenic varian...
INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by synaptic dysfunction and the accumulation of amyloid plaques. The molecular mechanisms linking gene dysregulation, pathogenic variants, and protein interaction networks to these core pathologies remain incompletely understood. This study aimed to integrate transcriptomic data with mutation and structural modeling to uncover disease mechanisms and identify therapeutic targets. METHODS: We performed differential gene expression analysis on the GSE138260 microarray dataset using GEO2R to identify DEGs in AD brain tissue. Missense mutations in DEGs were retrieved from the Alzheimer's Disease Variant Portal (ADVP). Protein-protein interaction networks were constructed using the STRING database to identify connections with the amyloid precursor protein (APP). Molecular dynamics simulations were conducted to evaluate the structural consequences of the BDNF V66M mutation. RESULTS: A total of 1,588 DEGs were identified, including upregulation of immune-related genes and downregulation of neuroplasticity-associated genes (e.g., BDNF, GRIN2B, GRM8). PPI analysis revealed a core network centered on APP, including BDNF as a direct interactor. The V66M variant in BDNF, confirmed to be downregulated in AD brains, showed increased rigidity and localized flexibility in structural models. DISCUSSION: The integration of transcriptomics and protein modeling revealed a critical link between BDNF dysfunction and APP interaction in AD. The V66M mutation was found to structurally alter BDNF, potentially disrupting its neuroprotective roles. The findings suggested that impaired BDNF signaling, driven by transcriptional repression and structural mutation, contributes to amyloid pathology and synaptic failure. CONCLUSION: This multi-omics investigation has identified BDNF as a converging point of gene dysregulation and pathogenic mutation within an APP-centric network. Structural alterations induced by the V66M mutation may exacerbate amyloid accumulation and neuronal dysfunction, supporting therapeutic strategies aimed at enhancing BDNF signaling in AD.
Integrative Perspectives on Neurodegeneration and Aging: From Molecular Insights to Therapeutic Strategies.
Ghosh S, Sinha JK
Curr Alzheimer Res · 2025 · PMID 41051050 · Publisher ↗
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Clinical Study on the Neuroprotective Effects of Dengzhan Shengmai Capsule on Brain Structure and Cognitive Function in Patients with Vascular Cognitive Impairment.
Li M, Wang D, Wei D … +4 more , Zhang J, Dai X, Zhang Z, Li H
Curr Alzheimer Res · 2025 Oct · PMID 41047680 · Publisher ↗
INTRODUCTION: Vascular Cognitive Impairment (VCI) is a common type of dementia that affects the quality of life and lacks effective treatments. The Dengzhan Shengmian capsule (DZSM), a traditional Chinese medicine, is cl...
INTRODUCTION: Vascular Cognitive Impairment (VCI) is a common type of dementia that affects the quality of life and lacks effective treatments. The Dengzhan Shengmian capsule (DZSM), a traditional Chinese medicine, is clinically used to alleviate VCI symptoms, but its therapeutic mechanisms are not fully understood. This study aimed to evaluate the neuroprotective effects of DZSM in VCI patients by investigating its impact on cognitive function and brain structure, thereby providing neuroimaging evidence for its clinical application. METHODS: A randomized, double-masked, 6-month trial was conducted with 100 VCI patients, assigned to either the experimental group receiving DZSM (n = 50) or the placebo group (n = 50). The efficacy of DZSM in VCI patients was assessed through cognitive behavioral assessments and neuroimaging data collected at baseline and after 6 months. A comparison was made across groups to determine cognitive and neural changes associated with the intervention. RESULTS: Participants receiving DZSM exhibited significant improvements across multiple cognitive domains compared to the placebo, including global cognition (MMSE, p = 0.019; ADASCog, p < 0.001), episodic memory (AVLT-N1N5, p < 0.001), visuospatial ability (CDT, p = 0.034), and working memory (DST, p = 0.015). For brain structure, the gray matter volume in the right postcentral and precentral gyrus, bilateral cuneus, left supplementary motor area, superior occipital gyrus, right hippocampus, right thalamus, bilateral lingual gyrus, left precuneus, right inferior frontal gyrus (triangular part), left inferior parietal gyrus, left superior medial frontal gyrus, right superior temporal gyrus, left middle temporal gyrus, and right parahippocampal gyrus increased in the DZSM group (FDR-corrected, p<0.05), with no significant changes in white matter microstructure. Moreover, gray matter volume increases positively correlated with improvements in global cognition and visuospatial function. DISCUSSION: DZSM capsules significantly improved multiple cognitive domains in VCI patients, particularly memory, visuospatial, and executive functions. The observed increases in gray matter volume suggest that DZSM may exert neuroprotective effects through structural brain remodeling, which is closely associated with cognitive enhancement. CONCLUSION: This study identifies brain structural abnormalities in VCI patients that correlate with cognitive deficits. DZSM capsule treatment significantly improved cognitive function. While the underlying mechanisms remain to be fully elucidated, these effects may be related to structural changes in the brain.
Research Progress on the Pathogenesis, Therapeutic Strategies, and Phthalocyanine Compounds for Alzheimer's Disease.
Wang R, Yang X
Curr Alzheimer Res · 2025 Oct · PMID 41047679 · Publisher ↗
Alzheimer's disease (AD) is a formidable and complex neurodegenerative disorder driven by multifactorial interactions, including amyloid-beta (Aβ) aggregation, neurofibrillary tangles, and neuroinflammation etc. Current...
Alzheimer's disease (AD) is a formidable and complex neurodegenerative disorder driven by multifactorial interactions, including amyloid-beta (Aβ) aggregation, neurofibrillary tangles, and neuroinflammation etc. Current therapies mainly consist of cholinesterase inhibitors and NMDA receptor antagonists, which can alleviate symptoms but fail to reverse disease progression. In recent years, emerging approaches such as immunotherapy and gene therapy have shown potential but remain in clinical exploration. Phthalocyanine (Pc) compounds, with their ability to inhibit Aβ fibril formation, favorable biocompatibility, and optical properties, have demonstrated potential in AD diagnosis and treatment. This review discusses the pathogenesis, therapeutic strategies, and research progress of Pc compounds in AD. Furthermore, the elucidation of their mechanisms of action, the optimization of blood-brain barrier penetration, and the promotion of clinical translation are needed to provide new directions for AD therapy.
Advancing Alzheimer's Disease Diagnosis Using VGG19 and XGBoost: A Neuroimaging-Based Method.
Boudi A, He J, Abd El Kader I … +2 more , Liu X, Mouhafid M
Curr Alzheimer Res · 2025 · PMID 40965073 · Publisher ↗
INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently affects over 55 million individuals worldwide. Conventional diagnostic approaches often rely on subjective clinical assess...
INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently affects over 55 million individuals worldwide. Conventional diagnostic approaches often rely on subjective clinical assessments and isolated biomarkers, limiting their accuracy and early-stage effectiveness. With the rising global burden of AD, there is an urgent need for objective, automated tools that enhance diagnostic precision using neuroimaging data. METHODS: This study proposes a novel diagnostic framework combining a fine-tuned VGG19 deep convolutional neural network with an eXtreme Gradient Boosting (XGBoost) classifier. The model was trained and validated on the OASIS MRI dataset (Dataset 2), which was manually balanced to ensure equitable class representation across the four AD stages. The VGG19 model was pre-trained on ImageNet and fine-tuned by unfreezing its last ten layers. Data augmentation strategies, including random rotation and zoom, were applied to improve generalization. Extracted features were classified using XGBoost, incorporating class weighting, early stopping, and adaptive learning. Model performance was evaluated using accuracy, precision, recall, F1-score, and ROC-AUC. RESULTS: The proposed VGG19-XGBoost model achieved a test accuracy of 99.6%, with an average precision of 1.00, a recall of 0.99, and an F1-score of 0.99 on the balanced OASIS dataset. ROC curves indicated high separability across AD stages, confirming strong discriminatory power and robustness in classification. DISCUSSION: The integration of deep feature extraction with ensemble learning demonstrated substantial improvement over conventional single-model approaches. The hybrid model effectively mitigated issues of class imbalance and overfitting, offering stable performance across all dementia stages. These findings suggest the method's practical viability for clinical decision support in early AD diagnosis. CONCLUSION: This study presents a high-performing, automated diagnostic tool for Alzheimer's disease based on neuroimaging. The VGG19-XGBoost hybrid architecture demonstrates exceptional accuracy and robustness, underscoring its potential for real-world applications. Future work will focus on integrating multimodal data and validating the model on larger and more diverse populations to enhance clinical utility and generalizability.
Effects of Cognitive Demand and Imaginability on Semantic Cognition in Patients with Primary Progressive Aphasia.
Ferrer Aragon J, Tellez-Alanis B, Hernandez-Galvan A … +1 more , Sosa Ortiz AL
Curr Alzheimer Res · 2025 · PMID 40965072 · Publisher ↗
INTRODUCTION/OBJECTIVE: Primary progressive aphasia (PPA) is a clinical syndrome characterized by progressive language impairment. Three subtypes have been identified: semantic (svPPA), nonfluent (nfPPA), and logopenic (...
INTRODUCTION/OBJECTIVE: Primary progressive aphasia (PPA) is a clinical syndrome characterized by progressive language impairment. Three subtypes have been identified: semantic (svPPA), nonfluent (nfPPA), and logopenic (lvPPA). Although clinical criteria exist to classify these subtypes, the specific ways in which semantic cognition is impaired across these variants have not yet been fully elucidated. This cross-sectional study aimed to analyze the effects of cognitive demand and imaginability on semantic cognition in patients with PPA. METHODS: Fifteen patients with PPA (five per variant) and 20 healthy controls completed a semantic association task comprising 20 items. The task included two levels of cognitive demand (low and high) and two types of concepts (concrete and abstract). Participants selected the word with the strongest semantic link to a probe word, based on synonymy, categorical relations, or shared features. Accuracy and reaction times were recorded and analyzed using nonparametric statistics. RESULTS: All PPA groups performed significantly worse than controls, showing fewer correct responses and longer reaction times. svPPA patients exhibited the greatest impairment across all conditions. nfPPA patients performed similarly to controls with concrete concepts but showed deficits with abstract words. lvPPA patients experienced greater difficulty under high cognitive demand, particularly with abstract words, indicating impaired semantic control. DISCUSSION: These findings suggest that svPPA is characterized by global impairment of conceptual knowledge, whereas nfPPA and lvPPA exhibit more selective deficits depending on concept type and cognitive demand. CONCLUSION: The research herein highlights the importance of considering cognitive demand and imaginability when assessing semantic cognition in PPA.
Unveiling Role of Gut Microbiota in Alzheimer's Disease: Mechanisms, Challenges and Future Perspectives.
Radhakrishnan P, Viswanathan K, Lini S … +2 more , Chinta S, Muthusamy S
Curr Alzheimer Res · 2025 · PMID 40965029 · Publisher ↗
Alzheimer's disease (AD) is a neurodegenerative condition characterized by neuroinflammation, tau hyperphosphorylation, Aβ (Amyloid beta) accumulation, and synaptic dysfunction. New research indicates that the gut-brain...
Alzheimer's disease (AD) is a neurodegenerative condition characterized by neuroinflammation, tau hyperphosphorylation, Aβ (Amyloid beta) accumulation, and synaptic dysfunction. New research indicates that the gut-brain axis, a network of two-way communication that involves immunological signals, neural pathways, and microbial metabolites, makes dysbiosis of the gut microbiota essential to the pathogenesis of AD. Alterations in the gut microbiota's composition hinder the production of crucial metabolites, such as short-chain fatty acids, trimethylamine- N-oxide, and secondary bile acids, which affect neuroinflammatory cascades, mitochondrial bioenergetics, and synaptic plasticity. Furthermore, Toll-like receptor 4 -4-mediated microglial responses are triggered by Gram-negative bacterial lipopolysaccharides. This cascade promotes oxidative stress, chronic neuroinflammation, and disruption of the (BBB) blood-brain barrier, all of which encourage the accumulation of neurotoxic proteins. Microbiome-modulating therapies, such as probiotics, prebiotics, and synbiotics, have been shown to have neuroprotective properties. They work by restoring microbial diversity, increasing (Short-chain fatty acids) SCFA-mediated anti-inflammatory pathways, and reducing glial activation. In addition to promoting gut microbiota equilibrium, dietary approaches like the Mediterranean and ketogenic diets, which are enhanced with polyphenols and omega-3 fatty acids, also lower systemic inflammation and increase neural resilience. Furthermore, the potential of postbiotics and fecal microbiota transplantation to attenuate AD-related neurodegeneration and restore gut-derived metabolic balance is being investigated. Translating these methods into standardized clinical applications is difficult, though, because individual microbiome composition varies. It will be essential to address these complications through mechanistic research and extensive clinical trials to establish gut microbiota as a promising therapeutic target in AD.
Arsenic Exposure Induces Cognitive Impairment in Mice with Increased Acetylcholinesterase Activity and Inflammation in the Cortex and Hippocampus: Implications for Alzheimer's Disease.
Dutta A, Phukan BC, Roy R … +3 more , Bhattacharya P, Kumar D, Borah A
Curr Alzheimer Res · 2025 · PMID 40926607 · Publisher ↗
INTRODUCTION: Arsenic, a metalloid, is well associated as a risk factor for the development and progression of neurodegenerative diseases, including Alzheimer's Disease (AD), which is characterized by impairment in cogni...
INTRODUCTION: Arsenic, a metalloid, is well associated as a risk factor for the development and progression of neurodegenerative diseases, including Alzheimer's Disease (AD), which is characterized by impairment in cognition. However, specific effects of arsenic on Acetylcholinesterase (AChE) activity and inflammatory markers in different brain regions, as well as its impact on behaviour, are not yet fully understood. METHODS: Arsenic was administered (20 mg/kg by gavage for 4 weeks) to male and female mice, and its effects on behaviour were assessed by using the object recognition memory test and lightdark box test. AChE activity and neuronal Nitric Oxide (nNOS) were assessed by histoenzymology, and immunohistochemistry was employed for assessment of Glial Fibrillary Acidic Protein (GFAP). RESULTS: Both the behavioural tests showed significant impairment of learning and memory functions and development of psychiatric abnormalities in arsenic-fed mice. The histoenzymology and immunohistochemistry analysis of the cortex and hippocampus region of these arsenic-fed mice revealed the increment of AChE activity and inflammatory markers, viz. GFAP and nNOS. DISCUSSION: The observed increment in AChE activity in the cortex and hippocampus of arsenic-fed mice may contribute to the impairment of learning and memory functions, as well as to the development of psychiatric abnormalities. Furthermore, the enhancement of inflammatory processes in these brain regions may be either a consequence or a contributing factor to the elevated AChE activity, thus establishing a self-fuelling cycle of neuroinflammation and increased AChE activity. CONCLUSION: Given the gender bias in neurodegenerative diseases, our findings indicate that arsenic exposure does not lead to significant differences in neuropathological and neurobehavioural outcomes between male and female mice. Moreover, current outcomes underscore the potential of arsenic to act as a neurotoxic agent in AD development.
Network Pharmacology of miR-146a-5p as a Potential Anti-Inflammatory Agent in Preventing Alzheimer's Disease.
Lee S, Foo J, Yong Y … +2 more , Daniel Looi Q, Ooi Y
Curr Alzheimer Res · 2025 · PMID 40916429 · Publisher ↗
INTRODUCTION: Alzheimer's disease is expressed as chronic neuroinflammation in the brain, which results in neuronal dysfunction, aberrant protein folding, and declining cognitive abilities. miR-146a-5p is a potent anti-i...
INTRODUCTION: Alzheimer's disease is expressed as chronic neuroinflammation in the brain, which results in neuronal dysfunction, aberrant protein folding, and declining cognitive abilities. miR-146a-5p is a potent anti-inflammatory agent that can attenuate several inflammatory diseases and promote wound healing. Our research aimed to utilize network pharmacology to elucidate the therapeutic potential of miR-146a-5p in treating Alzheimer's disease using a biocomputational approach. METHOD: Alzheimer's disease genes were extracted from DisGeNET, OMIM, and GeneCards databases. At the same time, miR-146a-5p candidate genes were sourced from four prediction databases: miRDB, miRWalk, miRNet, and TargetScan. RESULTS: The overlap between miR-146a-5p and Alzheimer's disease genes was established using STRING, with a score greater than 0.9, revealing a total of 157 nodes in the compound-target disease network. DISCUSSIONS: Pathway enrichment analysis further revealed key candidate genes associated with Alzheimer's, including those involved in neuronal death, leukocyte migration, and axon development. EGFR, IL6, NFKB1, TLR4, CXCL8, FN1, CXCR4, and BCL2 were pinpointed as the top 8 key candidate genes of miR-146a-5p. Between these key candidate genes, the miR-146a-5p Regulatory Network also demonstrated that miR-146a-5p downregulates EGFR and CXCR4. Furthermore, this research revealed the regulatory network of miR-146a-5p, which modulates the transcriptional activities of IL6, NFKB1, TLR4, CXCL8, FN1, and BCL2. CONCLUSION: Therefore, the current network pharmacology study explored the principal mechanism behind the anti-inflammatory effects of miR-146a-5p in treating Alzheimer's disease, and potentially to be applied to other neurodegenerative diseases.
The Association between the rs6656401 Locus of the CR1 Gene and Structural Alterations of Brain Effects in Han Chinese Patients with Alzheimer's Disease.
Zhou SY, Lin HX, Tang JM … +6 more , Yao QY, Hu JW, Long WJ, Dai WZ, Ma T, Zhu XC
Curr Alzheimer Res · 2025 · PMID 40916421 · Publisher ↗
INTRODUCTION: The complement receptor 1 (CR1) gene is identified as the one closely associated with Alzheimer's disease (AD). However, there has been no exploration of the imaging alterations associated with the CR1 gene...
INTRODUCTION: The complement receptor 1 (CR1) gene is identified as the one closely associated with Alzheimer's disease (AD). However, there has been no exploration of the imaging alterations associated with the CR1 gene in AD patients of the Han population. The purpose of this study is to investigate the association between the rs6656401 mutation and neuroimaging variations in Han AD patients. METHODS: We collected nuclear magnetic resonance images from 101 patients with AD and 98 healthy controls (HC). The subjects in this study, based on the different genotypes of rs6656401, were divided into three groups, with the number of AA, AG, and GG genotypes in the AD group being 1, 17, and 83, and 1, 8, and 89 in the HC group. Data were analyzed using the dominant model. Structural differences in the brain tissue between genotypes at the rs6656401 polymorphic locus were compared using voxel-based morphological analysis, cortical thickness, and graph-theoretic analysis to construct structural networks. RESULTS: Seven regions (namely, right precuneus, right caudal middle frontal cortical, right rostral middle frontal, right superior frontal, right bankssts, right superior parietal, and right paracentral) were significantly different across CR1 rs6656401 genotypes. The voxel-based morphometry analysis revealed that voxel cluster sizes in the left cerebellum, left superior temporal gyrus, right superior frontal gyrus orbital, right precuneus, and right superior parietal were significantly different in the AA, AG, and GG groups. The degree centrality (Dc) of the left inferior frontal gyrus was significantly greater in the GG group than in the AG group after false discovery rate correction in the structural network analysis. DISCUSSION: This study demonstrates that the rs6656401 AA genotype primarily induces structural alterations in the frontal, temporal, and parietal lobes of AD patients, with significant changes in the right middle frontal gyrus, precuneus, and superior parietal gyrus, along with Dc index alterations in the left inferior frontal gyrus affecting brain network function. Our findings confirm the association between the rs6656401 polymorphism and AD-related brain structural changes, providing the first evidence of these regional alterations in Han Chinese AD cohorts. Future studies will elucidate the locus's pathological mechanism to inform early diagnosis and targeted therapies. CONCLUSION: Our study first indicated that CR1 rs6656401 genotypes significantly influenced the morphological and structural covariate networks in Han AD patients.
Role of GSK-3 Inhibition in Alzheimer's Disease Therapy.
Algazzawi H, Abujamai J, Alshanberi AM … +2 more , Satar R, Ansari SA
Curr Alzheimer Res · 2025 Sep · PMID 40916410 · Publisher ↗
A serine/threonine kinase with a wide variety of substrates, Glycogen Synthase Kinase-3 (GSK-3) is widely expressed. GSK-3 is a key player in cell metabolism and signaling, modulating numerous cellular functions and play...
A serine/threonine kinase with a wide variety of substrates, Glycogen Synthase Kinase-3 (GSK-3) is widely expressed. GSK-3 is a key player in cell metabolism and signaling, modulating numerous cellular functions and playing significant roles in both healthy and diseased states. The two histopathological features of Alzheimer's disease, the intracellular neurofibrillary tangles composed of hyperphosphorylated tau, and the extracellular senile plaques composed of beta-amyloid, have been linked to GSK-3. It alters multiple tau protein locations found in neurofibrillary tangles. Additionally, GSK-3 can react to this peptide and regulate the production of beta-amyloid. The overexpression of GSK-3 in several transgenic models has been linked to tau hyperphosphorylation, neuronal death, and a reduction in cognitive function. It has been shown that lithium, a medication commonly used to treat affective disorders, inhibits GSK-3 at therapeutically relevant concentrations and stops tau phosphorylation. In this review, we provide an overview of the most recent research on the potential of GSK-3 inhibitors for treating Alzheimer's disease.
Topological Biomarkers of Alzheimer's Disease from Functional Brain Network Analysis.
Behrouzinia S, Khanteymoori A
Curr Alzheimer Res · 2025 · PMID 40873287 · Publisher ↗
INTRODUCTION: Alzheimer's disease is a progressive neurodegenerative condition characterized by the gradual deterioration of cognitive functions. Early identification of functional brain changes is crucial for timely dia...
INTRODUCTION: Alzheimer's disease is a progressive neurodegenerative condition characterized by the gradual deterioration of cognitive functions. Early identification of functional brain changes is crucial for timely diagnosis and effective intervention. This study employs multiplex network analysis to examine alterations in brain connectivity topology associated with Alzheimer's Disease, to identify early biomarkers and uncover potential therapeutic targets. METHODS: This study presents a secondary cross-sectional analysis based on a publicly available EEG dataset comprising spectral coherence measurements from 25 patients with clinically diagnosed Alzheimer's Disease (AD) and 25 age- and gender-matched Healthy Controls (HC). Functional connectivity matrices were generated across seven distinct frequency bands, with each brain region modeled as a network node and inter-regional coherence values represented as weighted edges. These matrices were then used to construct multiplex brain networks, which were rigorously analyzed using graph-theoretical approaches. The analysis encompassed key metrics, including modularity, centrality measures (Betweenness and MultiRank), motif distribution, and network controllability, to characterize and compare the underlying patterns of functional brain organization in AD and healthy aging. RESULTS: Networks associated with AD exhibited significantly reduced modularity, disrupted centrality patterns, and a higher occurrence of 2 and 3-node motifs, indicating local reorganization of connectivity. Additionally, the spatial distribution of driver nodes was markedly altered in AD. Centrality analyses revealed a pronounced shift in network hubs toward the temporal and insular cortices, suggesting compensatory or pathological reallocation of influence. Controllability assessments demonstrated a lower energy requirement for network control in AD, accompanied by increased inter-layer fragmentation, reflecting compromised integrative function across frequency bands. DISCUSSION: The findings revealed specific topological alterations, including reduced modularity, altered centrality, and decreased controllability, all of which are closely linked to AD-related network degeneration. By leveraging multi-frequency EEG data, the multiplex approach shows significant clinical potential for monitoring disease progression and supporting personalized treatments, with the ability to detect subtle connectivity disruptions before cognitive symptoms manifest. CONCLUSION: Multiplex network analysis reveals distinct and robust alterations in the functional brain architecture of individuals with Alzheimer's Disease. These network-level disruptions offer valuable insights into the pathophysiology of AD and highlight potential avenues for early diagnosis and targeted therapeutic strategies aimed at preserving cognitive function.
Neuropsychological Aspects of Sporadic Cerebral Amyloid Angiopathy: A Case Series and Narrative Review.
Pizzoni L, Cavalli A, Di Matteo F … +1 more , Mancini G
Curr Alzheimer Res · 2025 · PMID 40849758 · Publisher ↗
INTRODUCTION: Cerebral Amyloid Angiopathy (CAA) is a common form of cerebral small vessel disease (CSVD), characterized by the accumulation of amyloid-β (Aβ) protein in the walls of cortical and leptomeningeal arteries a...
INTRODUCTION: Cerebral Amyloid Angiopathy (CAA) is a common form of cerebral small vessel disease (CSVD), characterized by the accumulation of amyloid-β (Aβ) protein in the walls of cortical and leptomeningeal arteries and arterioles. The sporadic form primarily affects the elderly and is closely associated with Alzheimer's disease (AD). Despite previous studies on cognition, the specific neuropsychological profile of CAA remains unclear. This study aims to describe the cognitive profile of CAA patients and characterize their neuropsychological aspects in the absence of a clinical diagnosis of AD. METHODS: We present a case series of six patients with probable CAA, without clinical evidence of AD, who underwent extensive neuropsychological assessment. Additionally, a narrative review was conducted to synthesize current knowledge of the cognitive and neuropsychological aspects of sporadic CAA. RESULTS: The narrative review indicates that CAA predominantly affects executive functioning, processing speed, episodic memory, global cognition, and visuospatial functions. In our case series, all patients exhibited impairments in these domains, except for global cognition. Notably, a specific dissociation was observed in the Rey Auditory Verbal Learning Test (RAVLT), with impaired delayed recall but preserved recognition. DISCUSSION: Sporadic CAA in patients without AD contributes to cognitive impairment, particularly affecting executive functioning, processing speed, visuospatial functions, and episodic memory. In our sample, memory impairment in CAA follows a dysexecutive pattern, characterized by retrieval deficits with preserved storage. This contrasts with the amnestic profile seen in AD and amnestic mild cognitive impairment (aMCI), where both retrieval and storage are compromised. CONCLUSION: This distinct memory profile may represent a useful neuropsychological marker for differentiating CAA-related cognitive impairment from that associated with AD and its prodromal forms. This differentiation has potential implications for diagnosis, prognosis, and the development of tailored therapeutic strategies.
A DTI-Radiomics and Clinical Integration Model for Predicting MCI-to-AD Progression Using Corpus Callosum Features.
Yu W, Guo Y, Peng J … +5 more , Wang C, Zhang Z, Herrero MT, Tao M, Shu Z
Curr Alzheimer Res · 2025 Aug · PMID 40814882 · Publisher ↗
INTRODUCTION: This study aimed to explore the value of diffusion tensor imaging (DTI)- based radiomics in the early diagnosis of Alzheimer's disease (AD) and predicting the progression of mild cognitive impairment (MCI)...
INTRODUCTION: This study aimed to explore the value of diffusion tensor imaging (DTI)- based radiomics in the early diagnosis of Alzheimer's disease (AD) and predicting the progression of mild cognitive impairment (MCI) to AD. METHODS: A cohort of 186 patients with MCI was obtained from the publicly accessible Alzheimer's. Disease Neuroimaging Initiative (ADNI) database, and 49 of these individuals developed AD over a 5-year observation period. The subjects were divided into a training set and a test set in a ratio of 7 to 3. Radiomic features were extracted from the corpus callosum within the DTI post-processed images. The Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression algorithm was employed to develop radiomic signatures. The performance of the radiomic signature was assessed using receiver operating characteristic (ROC) analysis and decision curve analysis (DCA). RESULTS: In the training set, 35 patients were converted, and in the test set, 14 patients were converted. Among all the patients, notable differences were observed in age, CDR-SB, ADAS, MMSE, FAQ, and MOCA between the stable group and the transformed group (p < 0.05). In the test set, the AUCs of the radiomics signatures constructed based on fractional anisotropy, axial diffusivity, mean diffusivity, and radial diffusivity were 0.824, 0.852, 0.833, and 0.862, respectively. The AUC of the clinical model was 0.868, and that of the combined model was 0.936. DCA demonstrated that the combined model had the best performance. DISCUSSION CONCLUSION: The combined radiomics and clinical model, utilizing DTI data, can relatively accurately forecast which patients with MCI are likely to progress to AD. This approach offers potential for early AD prevention in MCI patients.
Multimodal Deep Learning Approaches for Early Detection of Alzheimer's Disease: A Comprehensive Systematic Review of Image Processing Techniques.
Amine JM, Mourad M
Curr Alzheimer Res · 2025 · PMID 40785178 · Publisher ↗
INTRODUCTION: Alzheimer's disease (AD) is the most common form of dementia, and it is important to diagnose the disease at an early stage to help people with the condition and their families. Recently, artificial intelli...
INTRODUCTION: Alzheimer's disease (AD) is the most common form of dementia, and it is important to diagnose the disease at an early stage to help people with the condition and their families. Recently, artificial intelligence, especially deep learning approaches applied to medical imaging, has shown potential in enhancing AD diagnosis. This comprehensive review investigates the current state of the art in multimodal deep learning for the early diagnosis of Alzheimer's disease using image processing. METHODS: The research underpinning this review spanned several months. Numerous deep learning architectures are examined, including CNNs, transfer learning methods, and combined models that use different imaging modalities, such as structural MRI, functional MRI, and amyloid PET. The latest work on explainable AI (XAI) is also reviewed to improve the understandability of the models and identify the particular regions of the brain related to AD pathology. RESULTS: The results indicate that multimodal approaches generally outperform single-modality methods, and three-dimensional (volumetric) data provides a better form of representation compared to two-dimensional images. DISCUSSION: Current challenges are also discussed, including insufficient and/or poorly prepared datasets, computational expense, and the lack of integration with clinical practice. The findings highlight the potential of applying deep learning approaches for early AD diagnosis and for directing future research pathways. CONCLUSION: The integration of multimodal imaging with deep learning techniques presents an exciting direction for developing improved AD diagnostic tools. However, significant challenges remain in achieving accurate, reliable, and understandable clinical applications.
Neuroprotective Effects of Fenugreek Leaf Extract in a Model of Alzheimer's Disease Expressing Human Aβ-42.
Varshney H, Gaur K, Subhan I … +6 more , Fatima J, Jyoti S, I M, Shahid M, Rahul, Siddique YH
Curr Alzheimer Res · 2025 · PMID 40785177 · Publisher ↗
INTRODUCTION: Much emphasis has been given to the biological activities of Fenugreek against various diseased conditions. This study investigated the effect of fenugreek leaf extract on behavioural and cognitive function...
INTRODUCTION: Much emphasis has been given to the biological activities of Fenugreek against various diseased conditions. This study investigated the effect of fenugreek leaf extract on behavioural and cognitive function of transgenic Drosophila having human Aβ-42 expression in the neurons, herein referred as Alzheimer's disease model flies (AD flies). METHODS: AD flies were exposed to four different doses of fenugreek leaf extract (FE) containing i.e., 0.005, 0.010, 0.015 and 0.02 g/ml for 30 days. Thereafter, behavioural and cognitive assessment was done using climbing ability, activity pattern, aversive phototaxis and odour choice indexes. The life span of different groups of flies was also recorded. The effect of FE on the oxidative stress markers, acetylcholinesterase, monoamine oxidase (MAO) and caspase 3 and 9 activities were determined. The deposition of Aβ-42 aggregates in the brain tissue of the flies was studied by performing immunostaining. Also, the metabolic profile of different groups of flies was studied by performing LC-MS/MS. Compared with control flies, 22 selected metabolites were found to be upregulated and downregulated among transgenic AD flies and FE exposed AD flies compared to control. RESULTS: The findings of this study showed the neuroprotective role of fenugreek extract, which could be employed for the treatment of Alzheimer's disease. The AD flies exposed to FE showed a dose-dependent postponement in the decline of climbing ability, activity and cognitive impairments. A significant dose dependent increase in the life span was also noticed in the AD flies exposed to FE. A significant reduction in the oxidative stress, acetylcholinesterase, monoamine oxidase, and caspase-3&9 activities was also observed in a dose dependent manner. The results obtained from the immunostaining suggest the reduction in the deposition of Aβ-42 fibril, which was also confirmed by the docking studies showed the energetically favoured interaction useful for inhibiting the acetylcholinesterase and Aβ-42 aggregates. DISCUSSION: This study demonstrates the neurological potency of fenugreek leaf extract (FE) in a Drosophila model of AD due to its antioxidantive, anti-cholinesterase, and neuroprotective properties. Using a combination of behavioral, biochemical, histological, and metabolomic approaches, we evaluated the therapeutic potential of FE in mitigating AD-like symptoms in transgenic flies expressing Aβ-42. CONCLUSION: Fenugreek leaf extract may serve as a potential natural remedy for slowing down or alleviating the progression of AD.
Unveiling the Potential Role of Cathinone and Cathine Compounds in Alzheimer's Disease: Predictive Insights.
Alkaf MS, Said MA, Algamdi NA … +1 more , Al-Kaff NS
Curr Alzheimer Res · 2025 · PMID 40760747 · Publisher ↗
INTRODUCTION: Khat (Catha edulis (Vahl) Forssk. ex Endl.), a stimulant plant native to Africa and Asia, contains psychoactive compounds such as cathinone and cathine that affect the central nervous system. This study aim...
INTRODUCTION: Khat (Catha edulis (Vahl) Forssk. ex Endl.), a stimulant plant native to Africa and Asia, contains psychoactive compounds such as cathinone and cathine that affect the central nervous system. This study aims to investigate the potential neurotoxicological risks associated with these compounds, particularly focusing on their possible relationship with neurodegenerative disorders like Alzheimer's disease (AD). The primary objective was to evaluate the toxicity of khat's main compounds and examine their molecular interactions with Monoamine Oxidase A (MAO-A), an enzyme implicated in the pathology of AD. METHODS: The toxicological profiles of cathinone, cathine, amphetamine, and the AD medication Donepezil were assessed using the Protox-3 server, which predicted toxicity class, potential for liver damage, carcinogenicity, immunotoxicity, mutagenicity, and cytotoxicity. Molecular docking studies were conducted to analyse the binding interactions of these compounds with MAO-A (PDB ID: 2Z5X). Binding affinities and key interacting residues were identified. The steric effects of the ligands within the enzyme's binding site were quantified by calculating the buried volume (%VBur) using the centroid of centres method. RESULTS: Protox-3 classified cathine and amphetamine as Class 3 toxicants (moderate toxicity), while cathinone and Donepezil were assigned to Class 4 (lower toxicity). Cathinone also demonstrated a moderate probability (0.64) of carcinogenicity. Molecular docking revealed that khat compounds had an average binding affinity of -5.81 ± 0.27 kcal/mol, which was lower than that of amphetamine (-6.10 ± 0.27 kcal/mol) and Donepezil (-7.80 ± 0.38 kcal/mol). Buried volume analysis indicated that khat compounds and amphetamine were more deeply embedded in the MAO-A binding site, correlating with stronger binding affinity. DISCUSSION: The computational results suggest that khat compounds exhibit moderate neurotoxic potential and interact with MAO-A in a manner that could be relevant to AD pathology. Although the binding affinities are lower than those of Amphetamine and Donepezil, they point to possible molecular-level interactions significant for neurodegeneration. Steric hindrance, as quantified by %VBur, appeared to influence binding strength, highlighting the importance of molecular fit within the active site. CONCLUSION: This study presents evidence of a potential molecular link between khat consumption and an increased risk of Alzheimer's disease. The findings underscore the necessity for further in vivo and epidemiological research, particularly in regions with high rates of khat use, to assess its long-term neurotoxic effects.
Exploring the Interconnections of Genetic, Lifestyle, and Epigenetic Influences on Brain Aging: A Comprehensive Review.
Mehrabadi S, Barati S
Curr Alzheimer Res · 2025 · PMID 40760746 · Publisher ↗
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, life...
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.
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