Flavonoids and Alzheimer's disease: reviewing the evidence for neuroprotective potential.

Neurodegeneration, which manifests as several chronic and incurable diseases, is an age-related condition that affects the central nervous system (CNS) and poses a significant threat to the public's health for the elderly. Recent decades have experienced an alarming increase in the incidence of neurodegenerative disorders (NDDs), a severe public health issue due to the ongoing development of people living in modern civilizations. Alzheimer's disease (AD) is a leading trigger of age-related dementia. Currently, there are no efficient therapeutics to delay, stop, or reverse the disease's course development. Several studies found that dietary bioactive phytochemicals, primarily flavonoids, influence the pathophysiological processes underlying AD. Flavonoids work well as a supplement to manufactured therapies for NDDs. Flavonoids are effective in complementing synthetic approaches to treat NDDs. They are biologically active phytochemicals with promising pharmacological activities, for instance, antiviral, anti-allergic, antiplatelet, anti-inflammatory, antitumor, anti-apoptotic, and antioxidant effects. The production of nitric oxide (NO), tumor necrosis factor (TNF-α), and oxidative stress (OS) are downregulated by flavonoids, which slow the course of AD. Hence, this research turned from preclinical evidence to feasible clinical applications to develop newer therapeutics, focusing on the therapeutic potential of flavonoids against AD.

Immune Checkpoint Inhibitors in Geriatric Oncology.

PURPOSE OF REVIEW: This manuscript will update prior reviews of immune checkpoint inhibitors (ICIs) in light of basic science, translational, and clinical discoveries in the field of cancer immunology and aging. RECENT FINDINGS: ICIs have led to significant advancements in the treatment of cancer. Landmark trials of ICIs have cited the efficacy and toxicity experienced by older patients, but most trials are not specifically designed to address outcomes in older patients. Underlying mechanisms of aging, like cellular senescence, affect the immune system and may ultimately alter the host's response to ICIs. Validated tools are currently used to identify older adults who may be at greater risk of developing complications from their cancer treatment. We review changes in the aging immune system that may alter responses to ICIs, report outcomes and toxicities in older adults from recent ICI clinical trials, and discuss clinical tools specific to older patients with cancer.

CytoDirect: A Nucleic Acid Nanodevice for Specific and Efficient Delivery of Functional Payloads to the Cytoplasm.

Direct and efficient delivery of functional payloads such as chemotherapy drugs, siRNA, or small-molecule inhibitors into the cytoplasm, bypassing the endo/lysosomal trapping, is a challenging task for intracellular medicine. Here, we take advantage of the programmability of DNA nanotechnology to develop a DNA nanodevice called CytoDirect, which incorporates disulfide units and human epidermal growth factor receptor 2 (HER2) affibodies into a DNA origami nanostructure, enabling rapid cytosolic uptake into targeted cancer cells and deep tissue penetration. We further demonstrated that therapeutic oligonucleotides and small-molecule chemotherapy drugs can be easily delivered by CytoDirect and showed notable effects on gene knockdown and cell apoptosis, respectively. This study demonstrates the synergistic effect of disulfide and HER2 affibody modifications on the rapid cytosolic delivery of DNA origami and its payloads to targeted cells and deep tissues, thereby expanding the delivery capabilities of DNA nanostructures in a new direction for disease treatment.

Self-Assembly of Hybrid Peptide-DNA Nanostructures using Homotrimeric Coiled-Coil/Nucleic Acid Building Blocks.

Peptides and DNA are two of the most commonly used self-assembling biological molecules for the construction of nanomaterials. However, there are only a few examples that combine these two self-assembly motifs as key structural elements in a nanostructure. We report on the synthesis of a peptide-DNA conjugate that self-assembles into a stable homotrimer based on the coiled-coil motif. The hybrid peptide-DNA trimer was then used as a novel three-way junction to link together either small DNA tile nanostructures, or to close up a triangular wireframe DNA structure. The resulting nanostructures were characterized by atomic force microscopy, and compared with a scrambled, non-assembling peptide as a control. These hybrid nanostructures enable the integration of peptide motifs and potentially bio-functionality with DNA nanostructures, and open the door to novel nano-materials that have the advantages of both molecules.

Compounds from the Petroleum Ether Extract of Wedelia chinensis with Cytotoxic, Anticholinesterase, Antioxidant, and Antimicrobial Activities.

Wedelia chinensis is a folk medicine used in many Asian countries to treat various ailments. Earlier investigations reported that the petroleum ether extract of the plant has potential biological activity, but the compounds responsible for activity are not yet completely known. Therefore, the current work was designed to isolate and characterize the compounds from the petroleum ether extract and to study their bioactivities. Four compounds including two diterepenes (-) kaur-16α-hydroxy-19-oic acid (1) and (-) kaur-16-en-19-oic acid (2), and two steroids ß-sitosterol (3), and cholesta-5,23-dien-3-ol (4) were isolated and characterized. Among the compounds, the diterpenes were found to have more biological activities than the steroidal compounds. Compound 1 showed the highest cytotoxicity with LC50 of 12.42 ± 0.87 µg/mL. Likewise, it possesses good antioxidant activity in terms of reducing power. On the contrary, compound 2 exerted the highest antiacetylcholinesterase and antibutyrylcholinesterase activity. Both the diterpenes showed almost similar antibacterial and antifungal activity. The identification of diterpenoid and steroid compounds with multifunctional activities suggests that W. chinensis may serve as an important source of bioactive compounds which should be further investigated in animal model for therapeutic potential in the treatment of different chronic diseases.

Green consumers' behavioral intention and loyalty to use mobile organic food delivery applications: the role of social supports, sustainability perceptions, and religious consciousness.

Consumer behavior in the food industry has undergone significant changes in recent years, largely driven by growing consumer awareness of environmental, technological, religious, and social concerns. As a result, organic food has emerged as a popular alternative to conventionally produced food. Many emerging nations, including Bangladesh, promote its consumption due to its perceived health and safety benefits. Despite this growing trend, there remains a need for more understanding of consumer behavior, particularly concerning their motivations for continuous purchases toward mobile organic food delivery applications. In order to fill this knowledge gap, this study looks at how six indirect predictors (emotional support, informational support, environmental consciousness, religious consciousness, trust, and technological consciousness) affect customer loyalty through the intention to use organic food. This study employed a purposive sampling technique (i.e., judgmental sampling) and collected data from 386 respondents across three cities in Bangladesh. Data analysis was conducted using SmartPLS 3 software. The study found that all predictors, except for technological consciousness, significantly influenced behavioral intention, which, in turn, significantly influenced loyalty. Additionally, the study revealed that the five predictors, excluding technological consciousness, indirectly influenced loyalty through behavioral intention. The results of this study add to the existing literature on organic food by extending social support theory to include consumers' primary motivations, such as environmental, religious, technological, and social consciousness, as predictors of loyalty to use mobile organic food delivery applications. The study highlights the importance of sustainable food consumption in promoting environmental protection, ensuring social justice, creating economic success, and providing valuable insights for implementers looking to expand the organic food market.

Polyphenolics with Strong Antioxidant Activity from Acacia nilotica Ameliorate Some Biochemical Signs of Arsenic-Induced Neurotoxicity and Oxidative Stress in Mice.

Neurotoxicity is a serious health problem of patients chronically exposed to arsenic. There is no specific treatment of this problem. Oxidative stress has been implicated in the pathological process of neurotoxicity. Polyphenolics have proven antioxidant activity, thereby offering protection against oxidative stress. In this study, we have isolated the polyphenolics from Acacia nilotica and investigated its effect against arsenic-induced neurotoxicity and oxidative stress in mice. Acacia nilotica polyphenolics prepared from column chromatography of the crude methanol extract using diaion resin contained a phenolic content of 452.185 ± 7.879 mg gallic acid equivalent/gm of sample and flavonoid content of 200.075 ± 0.755 mg catechin equivalent/gm of sample. The polyphenolics exhibited potent antioxidant activity with respect to free radical scavenging ability, total antioxidant activity and inhibition of lipid peroxidation. Administration of arsenic in mice showed a reduction of acetylcholinesterase activity in the brain which was counteracted by Acacia nilotica polyphenolics. Similarly, elevation of lipid peroxidation and depletion of glutathione in the brain of mice was effectively restored to normal level by Acacia nilotica polyphenolics. Gallic acid methyl ester, catechin and catechin-7-gallate were identified in the polyphenolics as the major active compounds. These results suggest that Acacia nilotica polyphenolics due to its strong antioxidant potential might be effective in the management of arsenic induced neurotoxicity.

In vitro anti-melanogenic effects of chimeric compounds, 2-(substituted benzylidene)-1,3-indanedione derivatives with a ß-phenyl-α, ß -unsaturated dicarbonyl scaffold.

Tyrosinase is considered a key contributor to melanogenesis, and safe, potent tyrosinase inhibitors are needed for medical and cosmetic purposes to treat skin hyperpigmentation and prevent fruit and vegetable browning. According to our accumulated SAR data on tyrosinase inhibitors, the ß-phenyl-α,ß-unsaturated carbonyl scaffold in either E or Z configurations, can confer potent tyrosinase inhibitory activity. In this study, twelve indanedione derivatives were synthesized as chimeric compounds with a ß-phenyl-α,ß-unsaturated dicarbonyl scaffold. Two of these derivatives, that is, compounds 2 and 3 (85% and 96% inhibition, respectively), at 50 µM inhibited mushroom tyrosinase markedly more potently than kojic acid (49% inhibition). Docking studies predicted that compounds 2 and 3 both inhibited tyrosinase competitively, and these findings were supported by Lineweaver-Burk plots. In addition, both compounds inhibited tyrosinase activity and reduced melanin contents in B16F10 cells more than kojic acid without perceptible cytotoxicity. These results support the notion that chimeric compounds with the ß-phenyl-α,ß-unsaturated dicarbonyl scaffold represent promising starting points for the development of potent tyrosinase inhibitors.

Complete genome sequence of a potential foot-and-mouth disease virus serotype O vaccine strain from Bangladesh.

One of the six sublineages of the dominant O/ME-SA/Ind2001 lineage of foot-and-mouth disease virus (FMDV), Ind2001BD1 has already spread throughout 14 countries, including Bangladesh. Here, we report the complete genome sequence of the potential serotype O vaccine strain BAN/TA/Dh-301/2016, which has been shown to provide protection against all the circulating serotype O viruses in Bangladesh. The viral genome is 8,211 nucleotide (nt) long with an open reading frame (ORF) of 6999 nt. The ORF is flanked by a 1098-nt-long 5'-UTR and a 114-nt-long 3'-UTR. Compared to the Indian FMDV serotype O vaccine strain O/India/R2/75 (AF204276), ten mutations were identified in the major antigenic sites of BAN/TA/Dh-301/2016 (MK088170.1).

Astaxanthin ameliorates prenatal LPS-exposed behavioral deficits and oxidative stress in adult offspring.

BACKGROUND: Prenatal maternal lipopolysaccharide (LPS) exposure leads to behavioral deficits such as depression, anxiety, and schizophrenia in the adult lives. LPS-exposure resulted in the production of cytokines and oxidative damage. On the contrary, astaxanthin is a carotenoid compound, showed neuroprotective properties via its antioxidant capacity. This study examines the effect of astaxanthin on the prenatal maternal LPS-induced postnatal behavioral deficit in mice. RESULTS: We found that prenatal LPS-exposed mice showed extensive immobile phase in the tail suspension test, higher frequent head dipping in the hole-board test and greater hypolocomotion in the open field test. All these values were statistically significant (p < 0.05). In addition, a marked elevation of the level of lipid peroxidation, advanced protein oxidation product, nitric oxide, while a pronounced depletion of antioxidant enzymes (superoxide dismutase, catalase and glutathione) were observed in the adult offspring mice that were prenatally exposed to LPS. To the contrary, 6-weeks long treatment with astaxanthin significantly improved all behavioral deficits (p < 0.05) and diminished prenatal LPS-induced oxidative stress markers in the brain and liver. CONCLUSIONS: Taken together, these results suggest that prenatal maternal LPS-exposure leads to behavioral deficits in the adults, while astaxanthin ameliorates the behavioral deficits presumably via its antioxidant property.

The antioxidant effect of astaxanthin is higher in young mice than aged: a region specific study on brain.

Astaxanthin is a potential antioxidant which shows neuroprotective property. We aimed to investigate the age-dependent and region-specific antioxidant effects of astaxanthin in mice brain. Animals were divided into 4 groups; treatment young (3 months, n = 6) (AY), treatment old (16 months, n = 6) (AO), placebo young (3 months, n = 6) (PY) and placebo old (16 months, n = 6) (PO) groups. Treatment group was given astaxanthin (2 mg/kg/day, body weight), and placebo group was given 100 µl of 0.9% normal saline orally to the healthy Swiss albino mice for 4 weeks. The level of non-enzymatic oxidative markers namely malondialdehyde (MDA); nitric oxide (NO); advanced protein oxidation product (APOP); glutathione (GSH) and the activity of enzymatic antioxidants i.e.; catalase (CAT) and superoxide dismutase (SOD) were determined from the isolated brain regions. Treatment with astaxanthin significantly (p < 0.05) reduces the level of MDA, APOP, NO in the cortex, striatum, hypothalamus, hippocampus and cerebellum in both age groups. Astaxanthin markedly (p < 0.05) enhances the activity of CAT and SOD enzymes while improves the level of GSH in the brain. Overall, improvement of oxidative markers was significantly greater in the young group than the aged animal. In conclusion, we report that the activity of astaxanthin is age-dependent, higher in young in compared to the aged brain.

Re-emergence of circulatory foot-and-mouth disease virus serotypes Asia1 in Bangladesh and VP1 protein heterogeneity with vaccine strain IND 63/72.

Foot-and-mouth disease virus (FMDV) serotypes O, A and Asia1 are responsible for significant number of disease outbreaks in Bangladesh; however serotype Asia1 has not been reported in circulation since 1996. The present investigation reports the detection of serotype FMDV Asia1 from local farms in 2012 and 2013 outbreaks. The farms were located in Jessore and Gazipur districts, and one of these farms was under vaccine control programme. Phylogenetic analysis of the complete VP1 gene revealed that FMDV Asia1 is under genetic lineage C having close similarity to the Asia1 sequences of Indian origin. The circulatory genotype Asia1 showed VP1 protein sequence heterogeneity of eight amino acid substitutions within the G-H loop with the vaccine strain [IND 63/72 (AY304994)] used in vaccination programme. ELISA assay revealed that, of seven, only one local field serum sample (cattle vaccinated 38 days earlier) was positive at a titre level of >2.4 (log10) but failed to protect the cattle from infection occurred by the virus. This investigation focused that the eight amino acid substitution in VP1 protein at G-H loop of the locally circulated FMDV serotype Asia1 strain may be a reason for current vaccination failure.

A systematic review of effectiveness and safety of different regimens of levonorgestrel oral tablets for emergency contraception.

BACKGROUND: Unintended pregnancy is a complex phenomenon which raise to take an emergency decision. Low contraceptive prevalence and high user failure rates are the leading causes of this unexpected situation. High user failure rates suggest the vital role of emergency contraception to prevent unplanned pregnancy. Levonorgestrel - a commonly used progestin for emergency contraception. However, little is known about its pharmacokinetics and optimal dose for use. Hence, there is a need to conduct a systematic review of the available evidences. METHODS: Randomized, double-blind trials were sought, evaluating healthy women with regular menstrual cycles, who requested emergency contraception within 72 h of unprotected coitus, to one of three regimens: 1.5 mg single dose levonorgestrel, two doses of 0.75 mg levonorgestrel given 12 h apart or two doses of 0.75 mg levonorgestrel given 24 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. RESULTS: Every trial under consideration successfully established the contraceptive effectiveness of levonorgestrel for preventing unintended pregnancy. Moreover, a single dose of levonorgestrel 1.5 mg for emergency contraception supports its safety and efficacy profile. If two doses of levonorgestrel 0.75 mg are intended for administration, the second dose can positively be taken 12-24 h after the first dose without compromising its contraceptive efficacy. The main side effect was frequent menstrual irregularities. No serious adverse events were reported. CONCLUSIONS: The review shows that, emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen. All the regimens studied were very efficacious for emergency contraception and prevented a high proportion of pregnancies if taken within 72 h of unprotected coitus. Single levonorgestrel dose (1.5 mg) can substitute two 0.75 mg doses 12 or 24 h apart. With either regimen, the earlier the treatment is given, the more effective it seems to be.

Neuroinflammation: Contemporary anti-inflammatory treatment approaches.

We investigated the idea of possible anti-inflammatory treatment approaches for inflammatory disorders in the CNS. The articles used for this review were searched through PubMed, PsycINFO, and Google scholar and published between January 2000 and July 2013. The CNS has its own type of defensive mechanism. The crosstalk between neurons and the immune system take place via small molecules called cytokines that are secreted from glial cells. Previous study suggested that the imbalance of cytokines facilitates the development of CNS disorders. For instance, the interleukin-6 level is raised in the astrocyte cell during depressive episodes, while axons are damaged by the activated lymphocytes and microglia in multiple sclerosis. Several studies demonstrated that cytokines and inflammatory compounds are closely linked to neuropsychiatric and neurodegenerative disorders. Here, we have accumulated and summarized evidence from those papers that support the anti-inflammatory treatment options for inflammatory CNS disorders.

Low dietary carbohydrate induces structural alterations in enterocytes of the chicken ileum.

We investigated the role of dietary carbohydrates in the maintenance of the enterocyte microvillar structure in the chicken ileum. Male chickens were divided into the control and three experimental groups, and the experimental groups were fed diets containing 50%, 25%, and 0% carbohydrates of the control diet. The structural alterations in enterocytes were examined using transmission electron microscopy and immunofluorescent techniques for ß-actin and villin. Glucagon-like peptide (GLP)-2 and proglucagon mRNA were detected by immunohistochemistry and in situ hybridization, respectively. Fragmentation and wide gap spaces were frequently observed in the microvilli of the 25% and 0% groups. The length, width, and density of microvilli were also decreased in the experimental groups. The experimental groups had shorter terminal web extensions, and there were substantial changes in the mitochondrial density between the control and experimental groups. Intensities of ß-actin and villin immunofluorescence observed on the apical surface of enterocytes were lower in the 0% group. The frequency of GLP-2-immunoreactive and proglucagon mRNA-expressing cells decreased with declining dietary carbohydrate levels. This study revealed that dietary carbohydrates contribute to the structural maintenance of enterocyte microvilli in the chicken ileum. The data from immunohistochemistry and in situ hybridization assays suggest the participation of GLP-2 in this maintenance system.

Evaluation of THz wave transmission performance in TOPAS-based heptagonal photonic crystal fiber (He-PCF).

PCF denotes photonic crystal fiber which is utilized for terahertz (THz) waveguides and cladding in the shape of a hexagon with two elliptical air apertures (AHs), which are discussed. Such differentiation is made: When the frequency is 1 THz, effective material loss (EML) to a minimum of 0.028 cm-1 has been achieved. Making use of the heptagonal photonic crystal fiber (He-PCF) architecture, every simulation result utilizing COMSOL Multiphysics software implements the perfectly match layer (PML) and finite element method (FEM) boundary conditions. The He-PCF fiber demonstrates an effective mode loss (EML) of 0.028 cm-1 that is negligible, a substantial effective area (EA) measuring 7.31 × 10-8 m2 and an 80 % power concentration encompassing the central area at 1 THz frequency. Furthermore, regarding crucial optical guiding aspects like confinement loss, dispersion, and modality, a small study with respect to power fraction along with effective mode area (EMA) has again been conducted. Here, He-PCF THz waveguide is anticipated to provide a notable improvement in the current design for the communication field. Moreover, our suggested the PCF demonstrates perception by a solitary mode, as indicated through the utilization of the V-parameter, across a range in frequency spanning among 0.80 and 3 THz. Thus, it is anticipated that the layout of He-PCF fibers will facilitate efficient transmission of terahertz (THz) signals in a variety of communication applications.

Quantification and description of photothermal heating effects in plasmon-assisted electrochemistry.

A growing number of reports have demonstrated plasmon-assisted electrochemical reactions, though debate exists around the mechanisms underlying the enhanced activity. Here we address the impact of plasmonic photothermal heating with cyclic voltammetry measurements and finite-element simulations. We find that plasmonic photothermal heating causes a reduction in the hysteresis of the anodic and cathodic waves of the voltammograms along with an increase in mass-transport limiting current density due to convection induced by a temperature gradient. At slow scan rates, a temperature difference as low as 1 K between the electrode surface and bulk electrolytic solution enhances the current density greater than 100%. Direct interband excitation of Au exclusively enhances current density by photothermal heating, while plasmon excitation leads to photothermal and nonthermal enhancements. Our study reveals the role of temperature gradients in plasmon-assisted electrochemistry and details a simple control experiment to account for photothermal heating.

Enhancing resilience in transnational E-commerce supply chains: Critical factors, perspectives and strategic action plan.

This study develops a hybrid model to investigate the factors affecting transnational e-commerce supply chain resilience (TNSCRE) by integrating the Entropy Weight Method (EWM), Simple Additive Weighting (SAW), and Interpretive Structural Modeling (ISM). The study identifies 36 critical factors categorized under supply chain adaptability, supply chain efficiency, and supply chain evolution, and five criteria are used to rank these factors. The EWM is used to calculate the relative weights of the criteria, and the SAW method is used to rank the factors based on their weighted scores. The ISM is then used to evaluate the interrelationships among the key factors. The research highlights the significance of several factors, such as the speed of supply chain disruption recovery, interactive collaboration, and response time to supply chain disruption. Sensitivity analysis was performed to assess the robustness of the findings. Finally, a SWOT analysis is conducted to develop a strategic action plan for addressing these significant factors. The study provides a comprehensive understanding of the factors that impact TNSCRE from the perspective of multiple stakeholders. The findings can help e-commerce business owners improve their existing supply chain resilience and achieve sustainable growth in the context of globalization.

Morphostructural studies of pure and mixed metal oxide nanoparticles of Cu with Ni and Zn.

Nano-scale interactions between pure metal or metal-oxide components within an oxide matrix can improve functional performance over basic metal oxides. This study reports on the synthesis of monometallic (CuO), bimetallic (CuO-NiO) and trimetallic (CuO-NiO-ZnO) oxide nanoparticles (NPs) via the co-precipitation method and investigation of morphostructural properties. All of the synthesized metal oxide NPs were calcined at 550 °C temperature and annealed under vacuum. In this work, we applied Scherrer formula, modified Scherrer equation, Williamson-Hall plots, and Halder-Wagner plots to calculate the average crystallite size. The XRD data analysis showed that average crystallite sizes of the as-synthesized metal oxide phases were between 4 nm and 76 nm and average diameters calculated from SEM image were between 15 nm and 83 nm. The XRD studies also disclosed that average crystallite size and lattice microstrain of the CuO phases remain almost same (43 nm-46 nm and 2.074×10-3 to 2.665×10-3) for pure CuO and mixed CuO-NiO; but in case of mixed CuO-NiO-ZnO it is found to decrease in size to 11 nm where lattice microstrain increases to 9.653×10-3. Line broadening of diffraction peaks from microstrain contribution was between 0.02 and 0.01. Degree of crystallinity (%) of CuO phases found to decrease from 81 to 71. Dislocation density of CuO phases found to increase from 6.63×10-4nm-2 to 12.68×10-3nm-2. X-ray density of CuO phases increased from 6.48 to 6.53 g/cm3. Where this calculated small dislocation density well agreed with the high crystallinity. Crystal structure and specific surface area were determined from lattice constants and X-ray density. These synthesized nanopowders showed the existence of monoclinic, cubic, and hexagonal phases. The obtained NPs of multi-metal oxide explained more than one phases with different size, shape, and morphology at nano scale.

Aducanumab anti-amyloid immunotherapy induces sustained microglial and immune alterations.

Aducanumab, an anti-amyloid immunotherapy for Alzheimer's disease, efficiently reduces Aß, though its plaque clearance mechanisms, long-term effects, and effects of discontinuation are not fully understood. We assessed the effect of aducanumab treatment and withdrawal on Aß, neuritic dystrophy, astrocytes, and microglia in the APP/PS1 amyloid mouse model. We found that reductions in amyloid and neuritic dystrophy during acute treatment were accompanied by microglial and astrocytic activation, and microglial recruitment to plaques and adoption of an aducanumab-specific pro-phagocytic and pro-degradation transcriptomic signature, indicating a role for microglia in aducanumab-mediated Aß clearance. Reductions in Aß and dystrophy were sustained 15 but not 30 wk after discontinuation, and reaccumulation of plaques coincided with loss of the microglial aducanumab signature and failure of microglia to reactivate. This suggests that despite the initial benefit from treatment, microglia are unable to respond later to restrain plaque reaccumulation, making further studies on the effect of amyloid-directed immunotherapy withdrawal crucial for assessing long-term safety and efficacy.