Aduhelm (aducanumab) / Neurimmune, Eisai - LARVOL DELTA

Add-on combination therapy with monoclonal antibodies: Implications for drug development. (PubMed, J Prev Alzheimers Dis) - "Three anti-amyloid monoclonal antibodies (MABs) including aducanumab, lecanemab, and donanemab have been approved by the FDA and lecanemab and donanemab are available in the US market and a variety of other national markets. Patient convenience in terms of formulation and timing of add-on therapies will be important to successful clinical implementation. Add-on therapies are an important step in addressing the complexity of AD and optimizing patient outcomes."

Journal • Alzheimer's Disease • CNS Disorders • GFAP

Directed evolution of drug-like Aβ conformation-specific antibodies. (PubMed, Front Immunol) - "Notably, we find that this approach yields robust isolation of IgGs with higher affinity, higher conformational specificity, and lower off-target binding than multiple clinical-stage Aβ antibodies, including aducanumab and crenezumab. This antibody engineering platform can be readily applied to generate conformational antibodies against diverse types of peptide and protein aggregates linked to human diseases."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

Comparative Efficacy and Safety of Symptomatic Therapy and Disease-modifying Therapy for Alzheimer's Disease: A Systematic Review and Network Meta-Analysis (Frontiers) - "Aducanumab significantly improved ADAS-cog scores compared with placebo (MD -5.97, 95%CI - 10.33, -1.61; SUCRA: 93.0%) and demonstrated notable improvements in ADCS-ADL scores (MD 4.99, 95%CI 2.27, 7.72; SUCRA: 98.6%). Memantine ranked highest for neuropsychiatric symptoms (SUCRA: 80.8%). Aducanumab also had the highest SUCRA for CDR-SB (91.5%) and showed moderate superiority in MMSE scores (MD 3.55, 95%CI 1.35, 5.75; SUCRA: 98.2%)."

Review • Alzheimer's Disease

Neuropathological changes and amyloid-related imaging abnormalities in Alzheimer's disease treated with aducanumab versus untreated: a retrospective case-control study. (PubMed, Lancet Neurol) - "Disproportionate Aβ clearance and ARIA-associated neuropathology localised to superficial cortical layers suggest a distinctive pattern of target engagement by aducanumab. These findings inform understanding and monitoring of similar Aβ-targeting therapies."

Journal • Retrospective data • Alzheimer's Disease • CNS Disorders • APOE • Aβ42 • CD68

Anti-Amyloid Therapies for Alzheimer's Disease: Progress, Pitfalls, and the Path Ahead. (PubMed, Int J Mol Sci) - "The FDA granted traditional approval to lecanemab in July 2023, and the European Medicines Agency approved it in late 2024 with specific genetic restrictions; meanwhile, donanemab received FDA approval in July 2024 and EMA marketing authorization just one month ago...Therefore, precise risk management based on APOE genotyping and the presence of cerebral amyloid angiopathy and cerebral microbleeds should be performed before therapy is initiated. The near-term agenda should prioritize the following areas of study: (1) biomarker-driven front-end triage (including emerging plasma assays); (2) ARIA-aware care pathways and shared decision making; (3) outcome-based coverage and rational pricing; (4) clinical trials that layer anti-amyloid therapy into combinatorial strategies targeting tau protein, neuroinflammation, and synaptic resilience."

Biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • APOE

NEW DISCOVERIES IN AMYLOID-RELATED IMAGING ABNORMALITIES WITH HEMORRHAGE AND ANTI-AMYLOID BETA MONOCLONAL ANTIBODIES (WCN 2025) - "(5)Amyloid Beta Clearance Rate. The risk of ARIA-H, from highest to lowest, is as follows: Donanemab, Aducanumab, Bapineuzumab, Lecanemab, Gantenerumab, Crenezumab, Solanezumab. This research enhances our understanding of ARIA-H and may guide future monoclonal antibody drug development, which may improve the cognition and overall prognosis of Alzheimer's disease patients."

Alzheimer's Disease • CNS Disorders

EFFICACY OF ANTI-AMYLOID-Β ANTYBODIES IN ALZHEIMER'S DISEASE: A NETWORK META-ANALYSIS OF COGNITIVE AND FUNCTIONAL OUTCOMES (WCN 2025) - "Background and Aims: Monoclonal antibodies against amyloid-β in Alzheimer's disease (AD) treatments show variable efficacy. Although Donanemab shows the highest cognitive and functional decline delay, it is not significant due to the low number of study. Solanezumab, gantenerumab 510 mg, and aducanumab demonstrates cognitive improvements on the ADAS-Cog 13-item scale. No anti-Aβ antibody showed a significant benefit in slowing functional decline."

Retrospective data • Alzheimer's Disease • CNS Disorders

THE RISK OF AMYLOID RELATED IMAGING ABNORMALITIES (ARIA) WITH FDA-APPROVED ANTI-AMYLOID MONOCLONAL ANTIBODIES: A SYSTEMATIC REVIEW AND META-ANALYSIS (WCN 2025) - "Background and Aims: The recent FDA-approved anti-amyloid monoclonal antibodies (mAbs) for Alzheimer's Disease, namely Aducanumab, Lecanemab, and Donanemab have been associated with Amyloid Related Imaging Abnormalities (ARIA), which may lead to serious adverse events. Our study highlights a significantly increased risk of ARIA-E and ARIA-H with the use of mAbs for Alzheimer's Disease, particularly in Apo E4 carriers. Hence, it is important to regularly monitor patients receiving these drugs, identify risk factors for serious adverse events, and to weigh the potential symptomatic improvements and risks. Further evaluation of these medications is warranted through RCTs."

Retrospective data • Review • Alzheimer's Disease • CNS Disorders

Use of monoclonal antibodies in Alzheimer's disease - a systematic review of phase III clinical trials (ECNP 2025) - "Current pharmacological treatments available in Portugal include cholinesterase inhibitors: Rivastigmine, Galantamine, Donepezil, and the N-methyl-D-aspartate (NMDA) receptor antagonist Memantine (2). There was insufficient evidence to conclusively determine the effectiveness of monoclonal antibodies in significantly delaying AD progression. While Aducanumab has shown some promise at higher doses in specific trials, inconsistencies across studies highlight the need for further investigation. The failure of Crenezumab, Gantenerumab, and Solanezumab to achieve meaningful clinical benefits underscores the challenges of targeting amyloid beta in AD therapy."

Clinical • P3 data • Review • Alzheimer's Disease • CNS Disorders • Dementia • Psychiatry

Pharmacological Interventions in Dementia (PubMed, No Shinkei Geka) - "In 2021, the first drug targeting Aβ, aducanumab, was launched in the USA. In Japan, lecanemab and donanemab are now available as monoclonal antibodies targeting Aβ...Furthermore, dementia is a major risk factor for delirium, which often occurs during the course of dementia. In this study, we introduce pharmacotherapy with anti-dementia drugs, BPSD treatment, and delirium."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder

Anti-amyloid monoclonal antibody therapies in Alzheimer's disease - a scoping review. (PubMed, Neuroscience) - "Across the sample, reductions in amyloid burden were frequently reported (10 trials), with a smaller subset of studies reporting significant cognitive and functional improvements (4 trials), primarily lecanemab and aducanumab in addition to one pooled analysis of solanezumab. This review highlights the need for rigorous, diverse, and patient-centered research. Addressing these gaps is critical in ensuring safe, effective, and equitable treatment for all patients living with Alzheimer's disease."

Journal • Review • Alzheimer's Disease • CNS Disorders • APOE

WHY YOUR ALZHEIMER'S DISEASE STUDY IS GOING TO FAIL (WCN 2025) - "The recent regulatory approval of aducanumab was met with controversy rather than celebration... We may never find a single mechanism that can be addressed through treatment that will provide the dramatic slowing and even improvements for those afflicted with AD we all hope for. Amyloid-targeting treatments have shown only mild slowing of progression, yet even failed studies suggest some effect. Effective treatment may require combining multiple mild-effect therapies."

Alzheimer's Disease • CNS Disorders

INCREASING THE INFLUENCE OF THE ALZHEIMER'S RESEARCH COMMUNITY IN SHAPING THE PUBLIC NARRATIVE AROUND AD INTERVENTIONS (WCN 2025) - "With 86% of Americans now getting news from digital sources, social media plays a major role in shaping public opinion on scientific topics, as seen during COVID-19 and the aducanumab approval... AD researchers must actively shape discussions around treatments by providing clear, accurate, and accessible information. Encouraging our communities to share reliable scientific updates will help counter misinformation and strengthen public understanding as new research emerges."

Alzheimer's Disease • CNS Disorders

Combinatorial therapy with low dose IL-2 & Amyloid Beta targeting antibody for Alzheimer's disease (Neuroscience 2025) - "Our novel mAb demonstrated higher selectivity for neurotoxic Aβ isoforms compared to FDA approved mAbs, Aducanumab and Lecanemab. Compared to mAb alone and IL-2 alone, combinatorial therapy significantly reduced brain infiltrating inflammatory Teff cells, improved cognitive function (Radial arm water maze), and decreased amyloid burden compared to mAb alone and IL-2 alone treatment groups. These results support a translational approach combining oAβ specific mAb therapy with Treg stimulating agents like IL-2 to achieve effective amyloid clearance with reduced neuroinflammatory side effects, offering a promising strategy to improve the safety and efficacy profiles of immunotherapy in AD."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Aβ, Tau, and FDG-PET synthesis from multi-contrast MRI using deep learning (Neuroscience 2025) - "Clinical Trial Registration Number NIH Grant R01 NS119593; Clinical Trial Registration Number NIH P51OD010425; With the FDA’s recent approval of the anti-amyloid antibodies lecanemab and aducanumab, the prospect of disease-modifying therapies for Alzheimer’s disease has become a clinical reality. These results highlight the possibility of synthesizing clinically relevant PET scans from multi-contrast MRI for the diagnosis and monitoring of Alzheimer’s disease progression, potentially bypassing the need for traditional PET imaging. This will make early screening of Alzheimer’s more accessible, and improve the efficacy of disease-modifying treatments which require early intervention."

FDG PET • Alzheimer's Disease • CNS Disorders

Alzheimer's disease: where do we stand now and what are the strategic interventions? (PubMed, Front Cell Neurosci) - "These hallmarks gave rise to the two main theories that have opened the way for available treatments, such as FDA-approved memantine, and Aβ (aducanumab, lecanemab) and tau immunotherapies. This includes physical exercise, a healthy diet, mindfulness, and cognitive stimulation, among others. All of the above analyses are critical to switch the focus to the prevention of AD."

IO biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Immunology

Mapping the Evolving Landscape of Lecanemab Research in Alzheimer's Disease: A Bibliometric Analysis. (PubMed, Eur J Pharmacol) - "The bibliometric and text mining analysis revealed trends in research investigating the correlation between lecanemab and AD. It analyzed the cooperation among countries, regions, and authors, highlighting recent research hotspots. These data offer objective insights for scientific research and clinical practice on lecanemab and AD. These findings provide a roadmap for prioritizing clinical trials, optimizing drug development strategies, and addressing knowledge gaps in amyloid-targeted therapies."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

Cleavable Antibody-Conjugated Aβ Specific Immune Exosome for Combination Alzheimer's Disease Immunotherapy. (PubMed, Angew Chem Int Ed Engl) - "Upon cleavage by overexpressed β-secretase, ATExo-cL-aA releases aducanumab antibody (aA) and exosomes derived from Aβ antigen-specific Tregs (ATExo), which jointly manage Aβ and inflammatory microglia, thereby synergistically eradicating Aβ and reducing pro-inflammatory responses. In AD mouse models, ATExo-cL-aA demonstrates efficient brain accumulation, robust Aβ removal, microglial normalization, neuroinflammation attenuation, and synaptic preservation, ultimately leading to improved cognitive function. These findings highlight ATExo-cL-aA as next-generation immunotherapeutics that transcend the limitations of conventional antibody-based treatments for AD."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation

Anti-Amyloid Monoclonal Antibodies for Alzheimer's Disease: Evidence, ARIA Risk, and Precision Patient Selection. (PubMed, J Pers Med) - "Recent U.S. Food and Drug Administration (FDA) approvals of anti-amyloid monoclonal antibodies (mAbs) aducanumab, lecanemab, and donanemab represent the first disease-modifying therapies for early AD. Optimal use requires biomarker confirmation of the amyloid, careful tau staging, and genetic risk assessment. While limitations remain, these therapies represent a pivotal step toward precision neurology and may serve as a foundation for multimodal strategies targeting tau, neuroinflammation, and vascular pathology."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Inflammation • APOE

Structural and Functional Determinants of ARIA-H Risk in Anti-Amyloid Monoclonal Antibodies: A Comparative Mechanistic Framework for Alzheimer's Immunotherapy Development. (PubMed, Curr Neuropharmacol) - "These findings establish a mechanistic framework for ARIA-H risk and provide concrete molecular predictors to guide antibody engineering strategies. Prioritizing mAbs with controlled amyloid clearance, C-terminal binding domains, and IgG1 frameworks may enhance therapeutic safety, advancing precision immunotherapy for Alzheimer's disease."

Journal • Alzheimer's Disease • CNS Disorders • Hematological Disorders

Efficacy of AD04, an aluminum-based vaccine adjuvant, in patients with early Alzheimer's disease: Post hoc analysis of AFF006 (NCT01117818), a proof-of-concept, phase 2 randomized controlled trial. (PubMed, J Alzheimers Dis) - P2 | "In addition, we examined the observed treatment benefits of AD04 in the context of effects observed in trials of aducanumab, donanemab, and lecanemab, monoclonal anti-Aβ antibodies that received regulatory approval for AD.ResultsThe global statistical test suggested a treatment benefit of AD04 versus ineffective AD02 arms, even after accounting for multiplicity (primary methodology p-value, 0.03; permutation test p-value, 0.02). Adjusting for multiplicity using permutation testing can determine whether post-hoc effects are worth pursuing, or unlikely to be confirmed. These analyses have motivated a follow-up prospective randomized controlled trial, ADVANCE (EudraCT 2022-003532-73), in which optimized AD04 dosing will be compared to placebo in early AD."

Journal • P2 data • Retrospective data • Alzheimer's Disease • CNS Disorders

Aggregation-Dependent Epitope Sequence and Modification Fingerprints of Anti-Aβ Antibodies. (PubMed, bioRxiv) - "The monoclonal antibodies Aducanumab, Lecanemab, and Donanemab have recently been approved as the first disease-modifying treatments for early AD, highlighting the clinical importance of their exact binding profiles. Together, this work provides the most comprehensive dataset to date on aggregation-dependent sequence and modification selectivity of Aβ-Abs. By integrating mutational, PTM, and aggregation contexts in a unified experimental framework, we establish a resource that enables rational selection of antibodies for research and diagnostic applications, and offers mechanistic insights that may inform the design and optimization of future therapeutic antibodies in AD."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for Mild Cognitive Impairment or Mild Alzheimer's Disease Undergoing Standard of Care Monoclonal Antibody (mAb) Therapy (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Ali Rezai | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

The structural foundations of anti-amyloid-β immunotherapies: Unravelling antibody-antigen interactions in Alzheimer's disease treatment. (PubMed, J Alzheimers Dis) - "BackgroundAnti-amyloid-β (Aβ) immunotherapies are emerging as treatments for Alzheimer's disease (AD).ObjectiveThis review examines the structure-activity relationships of anti-Aβ therapeutics tested in phase 3 trials.MethodsWe analyzed crystallographic data and molecular models to elucidate the Aβ binding mechanisms of donanemab, lecanemab, aducanumab, bapineuzumab, gantenerumab, solanezumab, and crenezumab.ResultsLecanemab recognizes minimally degraded Aβ missing 1-2 residues, avoiding common Aβ in circulation and further degraded material sequestered in plaques. This focal point may account for the significant cognitive effects of lecanemab. The structure of aducanumab suggests a broadly neutralizing role has evolved for natural immunity to AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Vascular Neurology • APOE

From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer's Disease Landscape. (PubMed, Medicina (Kaunas)) - "Aducanumab and Lecanemab are IgG1 monoclonal antibodies that retard the progression of AD. Novel monoclonal antibodies may halt the AD course. Advances in delivery systems across the BBB are promising for the efficacy of AD treatments."

Journal • Review • Alzheimer's Disease • CNS Disorders • Gene Therapies • Inflammation • Metabolic Disorders • APOE • Aβ42