Introduction/Background: Lecanemab, an anti-amyloid monoclonal antibody, significantly reduces amyloid markers and slows clinical decline in early Alzheimer’s disease (AD) clinical trials. We assessed our single-center experience with lecanemab, including evaluating efficacy and safety data as well as patient-reported outcomes of individuals from our single center treated with intravenous or subcutaneous lecanemab. Materials and Methods: We conducted a single-center, nested cohort study of early AD subjects on lecanemab (intravenous or subcutaneous) at our center. Participants had been initiated on lecanemab therapy as part of lecanemab Study 201 or Clarity AD, and then continued lecanemab treatment in our center. Data collection included patient demographic characteristics, efficacy (eg, CDR-SB), safety, and patient-reported outcomes from surveys. Results: At our center, 136 people were randomized to receive either lecanemab or placebo in either lecanemab Study 201 (lecanemab:53; placebo:16) or Clarity AD (lecanemab:37; placebo:30). Patients receiving lecanemab were more likely to have higher rates of stable or improved disease across efficacy assessments relative to placebo. There were no new long-term safety signals, and the most common adverse events for lecanemab patients were infusion-related reactions (36.2%), ARIA-H (25.9%), and ARIA-E (13.8%). Survey responses demonstrated high satisfaction with the subcutaneous lecanemab administration, including with treatment satisfaction (97%) and convenience (97%). All patients preferred subcutaneous over IV dosing, citing quickness, ease, and comfort. Discussion: Our single-center experience with long-term lecanemab treatment was similar to that observed in clinical trials. Conclusion: The subcutaneous lecanemab formulation was highly preferred by patients and care partners, with feedback highlighting reduced treatment burden and strong acceptability.
Introduction: Research has found that the disinfection byproduct Tetrachloro-1,4- Benzoquinone (TCBQ) in drinking water increases the risk of Alzheimer's Disease (AD). However, the mechanism by which TCBQ increases the risk of AD remains unclear. Methods: This study employs a comprehensive approach that includes network toxicology (PPI network, hub genes, KEGG analysis), Mendelian randomization, computational simulations (molecular docking and dynamics), and cellular experiments to systematically elucidate the neurotoxic mechanisms of TCBQ. Results: Key findings indicate that TCBQ induces neurotoxicity by activating the Toll-like receptor signaling pathway, AD, and the apoptosis pathway. All ligand-receptor docking energies are recorded at ≤ -1.8 kcal/mol, suggesting that TCBQ demonstrates a stable interaction with the targets. Molecular simulations confirm that TCBQ tightly binds to targets such as Caspase3 and TLR4. Mendelian randomization found that XDH, FABP3, IMPDH1, ACBD7, and CASP3 are common targets and play a potential role in AD. Immunofluorescence experiments revealed that APP expression increased after TCBQ treatment. Cellular experiments verified that TCBQ significantly upregulates the expression of inflammation- and apoptosis-related proteins, including IL-1B, MyD88, NFκB, TLR4, Cleaved-Caspase3, and Cyt C, leading to neuronal cell death. Notably, the TLR4 inhibitor effectively reversed the expression of these proteins and alleviated cell death. Discussion: The discussion indicates that TCBQ induces neurotoxicity by activating the TLR4 pathway and apoptotic signals, and Caspase3 is a potential co-target. TLR4 inhibitors can reverse protein alterations and cell death, suggesting that intervention in this pathway may alleviate TCBQrelated nerve damage. Conclusion: Our research provides a theoretical basis for the clinical assessment of potential neurotoxicity risks in populations exposed to TCBQ.
Introduction: To conduct the first systematic bibliometric analysis of global research on the relationship between Alzheimer's disease (AD) and apoptosis from 2007 to 2025. Methods: This study utilized the Web of Science Core Collection (WoSCC) and Scopus to retrieve literature from 2007 to 2025 concerning the role of apoptosis in Alzheimer's disease. Bibliometric analysis and visualization were performed using the CiteSpace, VOSviewer, SCImago Graphica, and Bibliometrix R software packages. Results: China produced the most papers (n=823), though co-authorship led to duplicate counting. Leading institutions included China Medical University and Huazhong University of Science and Technology; Harvard University had the highest academic impact. The Journal of Biochemistry was the most active and cited journal. Dr. Zhang Y was the most prolific author, and Dr. Wang H the most cited. Discussion: China and the United States are dominant contributors, but Chinese research remains domestically oriented with lower international citation impact. The Journal of Alzheimer's Disease serves as a key dissemination platform. Major research themes include Aβ-induced mitochondrial dysfunction, oxidative stress, tau hyperphosphorylation synergizing with apoptosis, and emerging multi-target therapies. Recent attention has shifted towards inflammation, synaptic impairment, and combined strategies. The vicious cycles between Aβ and oxidative stress, and between tau pathology and apoptosis, warrant further mechanistic investigation. Conclusions: This study provides a systematic summary of research on AD and apoptosis. β- amyloid (Aβ) and abnormal Tau phosphorylation are likely to remain central areas of focus for future research.
Introduction/Objective: Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) aggregation, making its inhibition a promising therapeutic strategy. This study evaluated the effects of two phenylalanine derivatives on Aβ aggregation and associated neurotoxicity. Methods: Interactions between Aβ monomer and two compounds (12a and 5g) were explored by molecular docking. The inhibitory effects of the compounds on Aβ aggregation were evaluated using a thioflavin-T (ThT) assay, transmission electron microscopy (TEM), and dot blot. The neuroprotective ability of the two compounds was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. Results: Docking analysis revealed that compounds 12a and 5g can bind to monomeric Aβ and identified the amino acids responsible for the interactions. The two compounds significantly reduced ThT fluorescence during the 48-hour incubation at all concentrations in ThT kinetics assays. The inhibitory effects were further confirmed in TEM. Both compounds suppressed Aβ oligomerization (reductions to 42.72% and 35.90% of the untreated control group, respectively). Furthermore, compound 5g, with a new structure, showed remarkable protection (cell viability increased to 97.86% of the control) against Aβ oligomer-treated human neuroblastoma SH-SY5Y cells, while having no intrinsic effect on cell viability. Discussion: Compounds 12a and 5g act as more specific Aβ oligomerization inhibitors than traditional polyphenols such as (-)-epigallocatechin-3-gallate (EGCG). The results may provide molecular insights for the rational design of potent Aβ aggregation inhibitors for AD therapy. Conclusion: This study demonstrates that phenylalanine derivatives hold great promise as novel AD therapeutic leads.
Introduction: The study aimed to compare plasma Epoxyeicosatrienoic Acid (EET) isomers (5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET) in patients with advanced-stage late-onset Alzheimer’s Disease (AS-LOAD) versus healthy controls matched by age and sex. materials and methods: 2. Materials and Methods 2.1. Study Population This study included 60 participants: 30 patients with AS-LOAD who were being followed at the Community Mental Health Center of the Nigde Training and Research Hospital, and 30 age- and sex-matched cognitively healthy volunteers recruited from the hospital’s outpatient clinics. The diagnosis of AD in the patient group was made according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), based on clinical psychiatric evaluation. The control group consisted of individuals without any psychiatric disorders, as confirmed by DSM-V criteria and clinical examination, who volunteered to participate in the study. All procedures were conducted in accordance with the ethical standards of the Declaration of Helsinki. This study was approved by the Nigde Omer Halisdemir University Non-Interventional Clinical Research Ethics Committee (Approval No: 2025/70). 2.2. Collection of Blood Samples Participants and their guardians were informed about the study, and written informed consent was obtained before blood collection. Five mL of blood was collected from each participant into sterile EDTA tubes. The blood samples were centrifuged at 3000 rpm for 10 minutes to separate plasma. Plasma samples were stored at -80°C until EET level analyses were performed. 2.3. Determination of Plasma EET Levels Before the LC-MS/MS experiment, standards for all compounds were purchased from Cayman Chemicals (Ann Arbor, MI). The formic acid, Millipore water, dichloromethane, methanol (MeOH), and ammonium formate used were LC-grade and were obtained from Merck (Darmstadt, Germany). Quantification of plasma EET levels was performed by a validated liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method in the research and development laboratory of Bome Trivitron Industry Products Foreign Trade Inc., as previously described by Duflot et al.[19]. LC-MS/MS analysis was conducted using a Shimadzu 8040 LC-MS/MS system (Shimadzu, Japan) equipped with an electrospray ionization (ESI) source operating in positive ion mode. This system was coupled with a Shimadzu Prominence UFLC system (Shimadzu, Kyoto, Japan), which included a DGU-20A3 degasser, a Nexera-X2 pump, a SIL-20ACHT temperature-controlled autosampler, and a CTO-20AC column oven. Chromatographic separation was performed on a Kinetex C18 column (2.6 μm particle size, 50 mm length × 3 mm inner diameter). Instrument parameters were set to maintain a column temperature of 30°C with a flow rate of 0.6 mL/min. A gradient elution method was employed using methanol/formic acid and ammonium formate/formic acid mixtures as the mobile phases. System control and data acquisition were performed using LabSolutions software, and quantification was conducted in multiple reaction monitoring (MRM) mode. Endogenous EETs were accounted for by normalizing analyte peak areas to zero via linear regression. Calibration curve slopes and linearity were determined from analyte-to-internal standard peak ratios at each spiked concentration. The results were evaluated against the standard calibration curve. 2.4. Statistical Analysis All statistical analyses were performed using IBM SPSS Statistics version 18. The Kolmogorov–Smirnov and Shapiro–Wilk tests were applied to assess the normality of data distribution. Depending on data distribution, comparisons between groups were conducted using the Kruskal–Wallis and Mann–Whitney U tests for nonparametric variables, and one-way ANOVA for demographic parameters such as age and sex. A p-value of ≤ 0.05 was considered statistically significant. Methods: In this cross-sectional case-control study, 30 patients with AS-LOAD were compared with 30 cognitively healthy (control) individuals. Plasma EET levels were analyzed by liquid chromatography coupled with Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS). results: The statistical analysis of the demographic characteristics of the AS-LOAD and healthy control groups is presented in Table 1. No statistically significant differences were observed between the control and AS-LOAD groups in terms of mean age or sex distribution (p > 0.05). In our study examining plasma EET levels in patients with AS-LOAD, we found that plasma concentrations of EET isomers (5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET) were significantly decreased in AS-LOAD patients compared with age- and sex-matched healthy controls (p < 0.05, Figure 1). Specifically, plasma levels of 14,15-EET (29.37 ± 25.65 vs. 90.80 ± 91.02 ng/dL), 11,12-EET (65.79 ± 38.65 vs. 240.1 ± 237.73 ng/dL), 8,9-EET (57.52 ± 6.46 vs. 144.58 ± 133.77 ng/dL), and 5,6-EET (7.31 ± 8.62 vs. 11.76 ± 11.32 ng/dL) were significantly lower in the patient group compared to the controls (Figure 1). Results: Plasma concentrations of all measured EET regioisomers were significantly lower in patients with AS-LOAD compared with controls. Significant reductions were observed for 14,15-EET (p = 0.007), 11,12-EET (p = 0.001), 8,9-EET (p = 0.007), and 5,6-EET (p = 0.011). Discussion: EETs are reportedly implicated in AD development, with most previous investigations using animal models and targeted enzymes involved in EET metabolism, particularly soluble epoxide hydrolase (sEH). Furthermore, no studies have specifically examined EET metabolism in patients with advanced AD. This study revealed defective EET signaling with consequent increased sEH activity in AS-LOAD, suggesting that decreased EET might contribute to tau-mediated neurodegeneration, oxidative stress, and neuroinflammation in these patients. Conclusion: This study emphasizes the crucial role of EETs in AD pathology. Targeting EET metabolism could offer a promising therapeutic strategy for preventing AD. Studies that track disease progression are therefore a prerequisite for delaying its disease onset; thus, larger-scale longitudinal studies are needed to confirm these findings.
