The complexity of Alzheiemer's disease: New frontiers DOI Creative Commons
Elka Stefanova

Medicinski podmladak, Journal Year: 2024, Volume and Issue: 75(5), P. 76 - 83

Published: Jan. 1, 2024

Alzheimer's disease (AD) represents one of the most significant challenges in field neurodegenerative diseases our time, with its increasing prevalence and lack curative treatments, which highlights urgent need for innovative therapeutic strategies. It is a progressive disorder characterized by cognitive decline, impaired daily functioning loss independence. Its pathology accumulation amyloid beta plaques neurofibrillary tau protein tangles brain, accompanied neuroinflammation synaptic dysfunction. Genetic factors, such as mutations genes APP, PSEN1 PSEN2, directly cause familial forms, while APOE e4 allele only contributes to an increased risk AD development. Advances identification validation reliable biomarkers from cerebrospinal fluid (CSF) blood hold great promise improving early diagnosis, monitoring progression, assessing response treatment not research but also clinical practice effort alleviate burden this devastating disease. Blood particular significantly improve diagnostic accuracy effectively simplify referral processes, diagnosis well timely access treatment. Ongoing efforts shaping integration various settings are paving way toward precision medicine AD. Research focused on development disease-modifying therapies that target underlying pathological mechanisms The current transformative period knowledge about important moment promises changes conditions light immunotherapy course Given potential barriers may impede therapy, expand options beyond specialized centers, CSF provide attractive option screening detection efficacy. This approach could be testable scenario how future implementation designed, treatments proven successful treating applied widespread use biomarkers.

Language: Английский

Comparative the efficacy and safety of Gosuranemab, Semorinemab, Tilavonemab, and Zagotenemab in patients with Alzheimer’s disease: a systematic review and network meta-analysis of randomized controlled trials DOI Creative Commons

Wenting Cai,

Hui Zhang,

Yan Wu

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 29, 2025

Objective The aim of this study was to compare the efficacy and safety anti-tau protein monoclonal antibodies for Alzheimer’s disease (AD). Tau aggregation, a key pathological feature AD, is closely associated with neurodegeneration cognitive decline. Targeting tau has emerged as promising therapeutic strategy. By investigating effects on function, progression, overall quality life in patients which can provide valuable insights into their potential option devastating neurodegenerative disorder. Methods randomized controlled trials (RCTs) Gosuranemab, Semorinemab, Tilavonemab, Zagotenemab (AD) were systematically searched across PubMed, Embase, Web Science Cochrane Library, up May 2024. control group included placebo. indicators change Mini Mental State Examination (MMSE), Clinical Dementia Rating Scale Sum Boxes (CDR-SB), Disease Assessment Scale-Cognitive (ADAS-Cog), Cooperative Study-Activities Daily Living (ADCS-ADL) from baseline until time observation. Statistical analysis conducted using Stata 14 RevMan 5.4. purpose data processing, including generating network evidence plots, surface under cumulative ranking curve (SUCRA) ranking, league funnel visually summarize evaluate relative effectiveness publication bias multiple interventions. Mean differences (MD) 95% confidence interval (95%CI) effect sizes analyze continuous variables. Results This encompassed six RCTs involving 2,193 patients. Semorinemab more effective than placebo MMSE ADAS-Cog scores (MDs ranging between 0.52 3.21; MDs 0.17 3.30). Placebo showed relatively good according SUCRA CDR-SB ADCS-ADL (75.7 79.5%). Tilavonemab exhibited similar that two indicators. lower incidence AE, SAE, fall, urinary tract infections placebo, statistically significant. Most results no statistical difference. Conclusion indicated antibodies, such promise terms managing AD. Further studies are needed confirm these findings, assess long-term effects, refine treatment protocols. Systematic review registration https://www.crd.york.ac.uk/prospero/#myprospero , CRD42024583388.

Language: Английский

Citations

1
Impact of Peripheral Inflammation on Blood–Brain Barrier Dysfunction and Its Role in Neurodegenerative Diseases DOI Open Access
Ana Isabel Beltrán-Velasco, Vicente Javier Clemente‐Suárez

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2440 - 2440

Published: March 9, 2025

The blood–brain barrier (BBB) is essential for maintaining brain homeostasis by regulating molecular exchange between the systemic circulation and central nervous system. However, its dysfunction, often driven peripheral inflammatory processes, has been increasingly linked to development progression of neurodegenerative diseases such as Alzheimer’s Parkinson’s. Emerging evidence suggests that gut–brain axis plays a key role in BBB integrity, with intestinal dysbiosis chronic inflammation contributing disruption through immune metabolic pathways. Furthermore, selective vulnerability specific regions dysfunction appears be influenced regional differences vascularization, activity, permeability, making certain areas more susceptible processes. This review explored mechanisms linking inflammation, gut microbiota, emphasizing their neurodegeneration. A comprehensive literature was conducted using Web Science, PubMed, Scopus, Wiley, ScienceDirect, Medline, covering publications from 2015 2025. findings highlight complex interplay microbiota-derived metabolites, signaling, underscoring need targeted interventions microbiome modulation, anti-inflammatory therapies, advanced drug delivery systems. heterogeneity across different necessitates region-specific therapeutic strategies. Despite advancements, critical knowledge gaps persist regarding precise underlying dysfunction. Future research should leverage cutting-edge methodologies single-cell transcriptomics organ-on-chip models translate preclinical into effective clinical applications. Addressing these challenges will crucial developing personalized approaches mitigate impact diseases.

Language: Английский

Citations

1
Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease DOI Creative Commons

Amin Mahmood Thawabteh,

Aseel Wasel Ghanem, Sara AbuMadi

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(21), P. 5131 - 5131

Published: Oct. 30, 2024

The most prevalent chronic neurodegenerative illness in the world is Alzheimer's disease (AD). It results mental symptoms including behavioral abnormalities and cognitive impairment, which have a substantial financial psychological impact on relatives of patients. review discusses various pathophysiological mechanisms contributing to AD, amyloid beta, tau protein, inflammation, other factors, while emphasizing need for effective disease-modifying therapeutics that alter progression rather than merely alleviating symptoms. This mainly covers medications are now being studied clinical trials or recently approved by FDA fall under treatment (DMT) category, alters targeting underlying biological DMTs focus improving patient outcomes slowing decline, enhancing neuroprotection, supporting neurogenesis. Additionally, amyloid-targeting therapies, tau-targeting neuroprotective others. evaluation specifically looked at studies FDA-approved novel Phase II III development were carried out between 2021 2024. A thorough US government database identified biologics small molecule drugs 14 agents I, 34 II, 11 might be completed 2028.

Language: Английский

Citations

7
Engineered Antibodies to Improve Efficacy against Neurodegenerative Disorders DOI Open Access
Sarfaraz K. Niazi, Zamara Mariam,

Matthias Magoola

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6683 - 6683

Published: June 18, 2024

Antibodies that can selectively remove rogue proteins in the brain are an obvious choice to treat neurodegenerative disorders (NDs), but after decades of efforts, only two antibodies Alzheimer’s disease approved, dozens testing phase, and one was withdrawn, other halted, likely due efficacy issues. However, these outcomes should have been evident since cannot enter sufficiently blood–brain barrier (BBB) protectant. all products be rejuvenated by binding them with transferrin, preferably as smaller fragments. This model tested quickly at a low cost applied bapineuzumab, solanezumab, crenezumab, gantenerumab, aducanumab, lecanemab, donanemab, cinpanemab, their paper demonstrates conjugating transferrin does not alter such amyloid-β (Aβ) α-synuclein. We also present selection conjugate designs will allow cleavage upon entering prevent exocytosis while keeping fragments connected enable optimal proteins. The identified readily returned patients lowest regulatory delays. These engineered manufactured recombinant engineering, mRNA technology, more affordable solution meet dire need effectively.

Language: Английский

Citations

6
The controversy around anti-amyloid antibodies for treating Alzheimer’s disease DOI Creative Commons

Philip Hunter

EMBO Reports, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Language: Английский

Citations

4
Safety and effectiveness of the anti‐amyloid monoclonal antibody (mAb) drug lecanemab for early Alzheimer's disease: The pharmacovigilance perspective DOI Creative Commons
Amy Bobbins, Miranda Davies, Elizabeth Lynn

et al.

British Journal of Clinical Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

The development of humanized IgG1 anti-amyloid monoclonal antibodies, such as lecanemab, provides a promising novel treatment pathway with potential disease-modifying effects for patients early Alzheimer's disease (AD). Lecanemab, which gained marketing approval by the United States Food and Drug Administration (US FDA) in July 2023, has since been approved multiple countries, including Kingdom (UK). decision UK's Medicines Healthcare products Regulatory Agency (MHRA) to approve lecanemab August 2024 followed similar regulatory decisions US Japan. However, at time approval, contrasted that European Medicine (EMA) 2024. Subsequently, EMA recommended November following re-examination further data submitted Marketing Authorisation Holder. National Institute Health Care Excellence (NICE) not use AD amid concerns, cost translation efficacy outcomes into clinically meaningful improvement. risks serious adverse events (SAEs), amyloid-related imaging abnormalities (ARIA), have also emerged from clinical trial concern rare, life-threatening events. This narrative review discusses requirement robust method monitoring safety effectiveness real-world setting considering recent decisions. Additionally, need evaluate proposed risk minimization measures (RMMs) is discussed resource constraints healthcare systems, those faced Service (NHS).

Language: Английский

Citations

0
The efficacy and safety of anti-amyloid monoclonal antibody versus acetylcholinesterase inhibitor with an in-depth analysis across genotypes and disease stages: a systematic review and meta-analysis DOI Creative Commons
Chih‐Wei Hsu, Tien‐Wei Hsu,

Yu‐Chen Kao

et al.

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown, P. 100195 - 100195

Published: May 1, 2025

To date, studies have not compared the efficacy and safety of monoclonal antibodies (mABs) with acetylcholinesterase inhibitors (AChEIs). Five electronic databases were systemic searched from inception to 10 November 2024 for double-blinded randomized controlled trial (RCT) patients diagnosed MCI or mild AD treated mABs AChEIs at least 6 months. The primary outcome was change in cognitive function, measured by Alzheimer's Disease Assessment Scale-cognitive subscale 14-item (ADAS-Cog) Clinical Dementia Rating Scale-Sum Boxes (CDR-SOB). secondary outcomes acceptability, tolerability, serious adverse events (SAE), all -cause mortality. For mABs, amyloid-related imaging abnormalities-edema (ARIA-E), abnormalities-hemorrhage (ARIA-H) also assessed. Subgroup analyses included (i) versus AD; (ii) without concomitant medications; (iii) Apolipoprotein E (ApoE4) carriers non-carriers. Data pooled using a random effects model within Bayesian framework. There 8010 participants (mean age: 71.5 years) across seven mAB trials, 4993 age:70.7 nine AChEI trials. When placebo, only AChEIs, associated slower progression decline on CDR-SOB difference -0.41 (95 % credible interval -0.61 -0.22); minimally important (MID) -1) ADAS-Cog (-1.35 (-2.36 -0.36), MID -2); however, these benefits did reach two measurements. Besides, (-0.30 (-0.60 -0.001)) than although differ outcomes, including SAE, all-cause Further analysis indicated that their disease stage, medications, APOE4 carrier status. However, homozygotes 5.53-fold (2.48 13.07) increased odds developing ARIA-E Finally, lecanemab demonstrated relatively better more favorable profile aducanumab donanemab. AChEIs; this effect MID. incidence status indicative treatment efficacy.

Language: Английский

Citations

0
Alzheimer’s Disease Immunotherapy and Mimetic Peptide Design for Drug Development: Mutation Screening, Molecular Dynamics, and a Quantum Biochemistry Approach Focusing on Aducanumab::Aβ2–7 Binding Affinity DOI Creative Commons
Victor L. B. França, Eveline M. Bezerra, Roner F. da Costa

et al.

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 20, 2024

Seven treatments are approved for Alzheimer's disease, but five of them only relieve symptoms and do not alter the course disease. Aducanumab (Adu) lecanemab novel disease-modifying antiamyloid-β (Aβ) human monoclonal antibodies that specifically target pathophysiology disease (AD) were recently its treatment. However, their administration is associated with serious side effects, use limited to early stages Therefore, drug discovery remains great importance in AD research. To gain new insights into development drugs a combination techniques was employed, including mutation screening, molecular dynamics, quantum biochemistry. These used outline interfacial interactions Aducanumab::Aβ

Language: Английский

Citations

3
A calmodulin-derived peptide TI-16 inhibits alzheimer's disease progression by decreasing aβ burden and restoring calcium dyshomeostasis DOI

Jingyang Su,

Jun Wei, Bowen Zhang

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108502 - 108502

Published: April 1, 2025

Language: Английский

Citations

0
Nanocarrier-mediated siRNA delivery: a new approach for the treatment of traumatic brain injury–related Alzheimer's disease DOI Creative Commons
Jie Jin,

Huajing Zhang,

Qianying Lu

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(9), P. 2538 - 2555

Published: Sept. 24, 2024

Traumatic brain injury and Alzheimer’s disease share pathological similarities, including neuronal loss, amyloid-β deposition, tau hyperphosphorylation, blood–brain barrier dysfunction, neuroinflammation, cognitive deficits. Furthermore, traumatic can exacerbate disease-like pathologies, potentially leading to the development of disease. Nanocarriers offer a potential solution by facilitating delivery small interfering RNAs across for targeted silencing key genes implicated in Unlike traditional approaches neuroregeneration, this is molecular-targeted strategy, thus avoiding non-specific drug actions. This review focuses on use nanocarrier systems efficient precise siRNAs, discussing advantages, challenges, future directions. In principle, siRNAs have target all non-targetable proteins, holding significant promise treating various diseases. Among therapeutic currently available neurological diseases, siRNA gene precisely “turn off” expression any at genetic level, radically inhibiting progression; however, challenge lies delivering barrier. Nanoparticles received increasing attention as an innovative tool treatment They are considered strategy with advantages being able cross barrier, delivery, enhanced stability, multifunctional therapy. The nanoparticles deliver specific modified injured gradually recognized feasible effective approach. Although still preclinical exploration stage, it expected achieve clinical translation future, creating new field molecular therapy precision medicine associated injury.

Language: Английский

Citations

2