Aduhelm (aducanumab) / Neurimmune, Eisai - LARVOL DELTA

Efficacy and safety of aducanumab, lecanemab, and donanemab in Alzheimer's disease: A meta-analysis of randomized controlled trials. (PubMed, J Alzheimers Dis) - "Brain-volume loss, ventricular enlargement, and treatment-related deaths were narratively identified but not pooled.ConclusionsAducanumab, lecanemab, and donanemab showed statistically significant but small slowing of decline that may not reach patient-perceptible clinical meaningfulness. Increased ARIA risk and additional safety signals support cautious selection, imaging surveillance, and individualized risk-benefit discussions."

Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Dementia • APOE

Differential Induction of ARIA-like Pathologies by Anti-Aβ Immunotherapies in 5XFAD Mice: A Comprehensive Analysis of 12-Weeks Dosing with Clinical-Stage Antibodies (Neuroscience 2026) - " We treated 8-month-old 5XFAD mice (n=5-10 group) for 12 weeks with weekly (QW) intraperitoneal injections of: 1) Isotype-mIgG2 control, 2) 3D6-mIgG2 (murine precursor of bapineuzumab), 3) Aducanumab-mIgG2 (humanized), or 4) Remternetug-mIgG2 (humanized). This head-to-head study in a robust amyloidosis model demonstrates that the risk of inducing ARIA-like pathology is highly dependent on the specific antibody's properties. These preclinical findings provide critical mechanistic insights into ARIA pathogenesis and underscore the importance of antibody screening for mitigating treatment-emergent adverse events."

Preclinical • Alzheimer's Disease • CNS Disorders

Improved preclinical Outcomes by Combinatorial Treg stimulating agent and Anti-Aβ mAb Therapy (Neuroscience 2026) - "This has led to market withdrawal of one approved anti-Aß mAb, Aducanumab.There is an urgent need to develop Aß-targeting immunotherapies that enhance amyloid clearance while minimizing neuroinflammatory responses...The binding profile was comparable to Lecanemab...The combination of 2CD3M Aß mAb with low dose IL-2 enhanced amyloid clearance, mitigated microgliosis, neuroinflammation and improved behavioral outcomes when compared to mAb or low dose IL-2 alone. This offers a clinically translatable approach to enhance mAb therapies for AD and supports the further development of this novel translational immunotherapy."

Preclinical • Alzheimer's Disease • CNS Disorders • Dementia

Multi-omic characterization of brain and biofluid responses to aducanumab and verubecestat in an amyloid mouse model (Neuroscience 2026) - "Finally, we note the aducanumab response was largely similar to treatment with the immunoglobulin control. These results showcase the utility of pharmacogenomic approaches in preclinical animal testing of candidate therapeutics, and highlight the broad and often adverse molecular consequences of candidate anti-amyloid treatments."

Preclinical • Alzheimer's Disease • CNS Disorders • APOE

Antiamyloid Antibody Effects on Aβ-42 Protein Aggregates Profiled Using Nanospectroscopy. (PubMed, Chem Biomed Imaging) - "Importantly, neither aducanumab nor lecanemab was observed to induce any surface adsorption-driven disassembly of Aβ-42 protofibrils or elongated mature fibrils. Thus, nanospectroscopy enables direct characterization of antibody-amyloid interfacial interactions and provides insights into the distinct modes of action of emerging anti-Aβ therapeutics through label-free chemical imaging."

Journal • Alzheimer's Disease • CNS Disorders

Pharmacological and Clinical Heterogeneity of Anti-Amyloid Monoclonal Antibodies in Early Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Trials. (PubMed, Med Sci (Basel)) - "PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for phase III placebo-controlled trials evaluating lecanemab, donanemab, aducanumab, and gantenerumab in patients with mild cognitive impairment due to AD or mild AD dementia with biomarker confirmation of amyloid pathology. The benefit-risk profile appears heterogeneous across individual antibodies and may reflect pharmacological differences in amyloid targeting and clearance mechanisms. These findings support cautious, individualized use of anti-amyloid therapies and highlight the need for longer-term studies to determine whether short-term slowing of decline translates into clinically meaningful disease modification."

Biomarker • Clinical • Heterogeneity • Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Hematological Disorders

Landscape of Apolipoprotein (APOE) in the Emirati Population and Recommendations for a Genotyping Approach for Amyloid-Beta Monoclonal Antibodies (Aβ-mAbs) in Alzheimer's Disease Patients. (PubMed, Cureus) - "APOE profiling supports genotype-informed treatment strategies for anti-amyloid therapies. These findings establish a population-specific framework for integrating genetic information into the Emirati Genome Program pharmacogenomic report, enhancing precision medicine approaches for AD management in the UAE."

Journal • Alzheimer's Disease • CNS Disorders • APOE

Sustaining Drug Discovery Amid the Limits of Alzheimer's Disease Immunotherapies. (PubMed, eNeuro) - "Here, the critical barriers that limit the impact of anti-amyloid immunotherapies, including aducanumab, lecanemab, and donanemab, are discussed. Emerging evidence of accelerated brain atrophy and immunotherapy tolerance further complicates benefit-risk consultation. Sustaining drug- discovery pipelines by exploring combination therapies, tau-targeted approaches, drug repositioning, and novel small molecules through will be essential to provide comprehensive treatment options and personalized treatment plans for affected patients."

Journal • Review • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Dementia • Hematological Disorders • APOE

Comparative risk of amyloid-related imaging abnormalities with anti-amyloid-β monoclonal antibodies: A systematic review and penalized likelihood network meta-analysis of randomized trials. (PubMed, J Alzheimers Dis) - "The highest ARIA-E risk was seen with donanemab and aducanumab, followed by gantenerumab and lecanemab. APOE ε4 carriage significantly elevated ARIA-E (OR 2.28) and ARIA-H (OR 2.07) risk, with a clear gene-dose effect in homozygotes.ConclusionsARIA risk varies substantially across anti-amyloid-β therapies and is strongly modulated by APOE ε4 status. These findings support genotype-informed risk stratification and individualized MRI monitoring to optimize the benefit-risk balance of disease-modifying therapies in AD."

Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Hematological Disorders • APOE

Anti-amyloid nanobody-Fc fusion protein drives potent amyloid clearance through microglial recruitment. (PubMed, Alzheimers Dement (N Y)) - "Our findings demonstrate that Fc effector function is indispensable for microglial-mediated amyloid clearance in vivo. By clarifying this fundamental mechanism, this study provides a framework for the rational design of next-generation immunotherapies. Furthermore, 2D10-Fc represents a promising therapeutic candidate, combining the high-affinity targeting of nanobodies with the effector power necessary for robust plaque clearance."

Journal • Alzheimer's Disease • CNS Disorders • APP

Clinicopathologic Evaluation of Amyloid Clearance in Alzheimer Disease. (PubMed, JAMA) - "To determine the postmortem and in vivo association between amyloid levels and downstream neuropathology after treatment with aducanumab in a patient with patchy areas showing minimal residual amyloid levels...In addition, amyloid clearance appears to preferentially occur in the gyral crests. Future studies should evaluate the differential mechanisms involved in amyloid clearance from superficial and deep cortical layers and in gyri and sulci because extensive amyloid clearance may be necessary to achieve downstream neuropathologic benefit after removal of amyloid."

Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Anti-amyloid immunotherapy drives APOE4 specific increases in glial reactivity, perivascular immune activation, and ARIA-like events. (PubMed, bioRxiv) - "9-month-old E2, E3, and E4FAD mice received weekly injections of chimeric Aducanumab (chAdu) or IgG control for 12 weeks, to assess APOE isoform-specific effects on amyloid dynamics, ARIA-H-like microhemorrhages, and underlying cellular and transcriptomic responses...Additionally, vascular branching analysis and parallel single cell and spatial transcriptomics revealed a loss of vascular plasticity and increased inflammatory and immune signaling in the neurovascular units of E4FAD mice. Together, these findings suggest the cerebrovasculature of E4s is uniquely susceptible to antibody mediated vascular damage and provide immunological targets for the assessment or mitigation of ARIA risk in this highest need population."

IO biomarker • Journal • Alzheimer's Disease • Amyloidosis • CNS Disorders • Hematological Disorders • APOE

Predicting cognitive function in Alzheimer's clinical trials via amyloid β-protein biomarkers. (PubMed, Br J Clin Pharmacol) - "This study clarified the correlation and established predictive models for CDR-SB and ADAS-COG-11 based on amyloid imaging. This research identifies potential biomarkers and model-derived benchmarks for future dose selection and decision-making in Alzheimer's drug development, potentially accelerating the development of new treatments."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Molecular mechanisms underlying amyloid lowering by aducanumab: differential and comparative effects of sex and IgG reveal the post-treatment disease brain. (PubMed, bioRxiv) - "These findings demonstrate sex-dependent PK and pharmacodynamic responses to chAdu, identify biologically meaningful IgG-driven effects, and reveal molecular signatures that persist after amyloid reduction. This work provides biological insights into pathways that may remain insufficiently addressed following amyloid lowering; revealing novel targets for future drug discovery to prevent and treat disease."

Journal • Alzheimer's Disease • CNS Disorders • Aβ42

Regional Amyloid Clearance By Aducanumab Is Associated With Greater Cortical Preservation At Autopsy (AAIC 2026) - No abstract available

Biological Pathways Associated With Amyloid-related Imaging Abnormalities Following Aducanumab Treatment (AAIC 2026) - No abstract available

Apoe4 Drives Changes In Glial Reactivity After Aducanumab Immunotherapy (AAIC 2026) - No abstract available

Effects Of Aducanumab On Behavior And MRI Findings In EC-APP770+/AppNL-G-F Mice (AAIC 2026) - No abstract available

Preclinical

FDA Approval of Donanemab-azbt: A New Dawn in Alzheimer's Disease Treatment. (PubMed, Health Sci Rep) - "Acetylcholinesterase inhibitors (AChEIs) such as donepezil, galantamine, and rivastigmine are commonly used to enhance cognitive function by increasing acetylcholine levels, but they can cause side effects like nausea, bradycardia, and headaches. NMDA receptor antagonists, like memantine, reduce glutamatergic activity and are used to manage symptoms, yet are also associated with adverse effects including dizziness and agitation. Recently, monoclonal antibodies such as aducanumab have been developed to target amyloid-beta aggregates, though they are associated with amyloid-related imaging abnormalities (ARIA)...However, its use may result in ARIA and other adverse effects, necessitating careful clinical and radiological monitoring during treatment. Despite the risks of ARIA and other adverse events, Donanemab-azbt represents a promising addition to AD therapy, offering the potential for improved outcomes in patients with early symptomatic disease and expanding the..."

FDA event • Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Pain

Neuroinflammation-centered pathophysiology and therapeutic strategy design in Alzheimer's disease: Cutting-edge developments. (PubMed, Cell Signal) - "Recent FDA approvals of anti-amyloid monoclonal antibodies, including aducanumab and lecanemab, represent important advances toward disease-modifying therapy, although their long-term clinical impact and safety profiles remain under evaluation. This review synthesizes current understanding of AD pathogenesis through an inflammation-centered framework, highlighting clinically actionable immune pathways and stage-specific therapeutic windows. By integrating mechanistic insights with biomarker-driven strategies, we aim to delineate translational paths toward more precise, safe, and clinically meaningful disease modification."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • NLRP3

Neuropathological study of the effects of aducanumab anti-Aβ immunotherapy on patients with Alzheimer's disease. (PubMed, Acta Neuropathol) - "The selective reduction of neuritic, but not neurofibrillary tangle phospho-tau implies that Aβ-targeted antibodies such as aducanumab alleviate plaque-associated dystrophy but may not address established tangles. This study describes the long-term outcomes of anti-Aβ immunotherapy in AD."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • APOE

Worth their weight in gray matter? A narrative review of cost-effectiveness analyses of monoclonal antibodies for Alzheimer's disease. (PubMed, Alzheimers Dement (N Y)) - "ICER variability across studies, despite reliance on the same clinical trials, reflects sensitivity to assumptions and potential sponsorship bias. Evidence is limited by small numbers of CEAs, reliance on modeled rather than real-world data, and absence of formal risk-of-bias scoring for individual CEAs. The cost-effectiveness of AD mAbs in the US context remains uncertain."

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

Dead-Space Microdomains as Explicit Barriers to Extracellular Drug Transport in Alzheimer's Disease. (PubMed, Pharm Res) - "The proposed framework provides a computationally efficient foundation for predictive multiphysics modeling in the human CNS and demonstrates how local ECS obstructions can lead to therapeutic hindrance in AD."

Journal • Alzheimer's Disease • CNS Disorders

Immunotherapeutic Innovations in Alzheimer's Disease: A Bibliometric Landscape of Global Research Trends and Evolution. (PubMed, Curr Neuropharmacol) - "Immunotherapy demonstrates disease-modifying potential in early-stage AD; however, it requires carefully optimized dosing regimens, precise biomarker-guided patient stratification, and integrated combinatorial strategies targeting Aβ, tau, and neuroinflammation. Future research should prioritize establishing robust translational models and promoting interdisciplinary collaboration to address preclinical-clinical translation gaps effectively."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • Immune Modulation • Immunology • Inflammation • NLRP3

Understanding quantitative effects of anti-amyloid therapies on tau biomarkers and functional outcome. Insights from a comprehensive mechanistic quantitative systems pharmacology study. (PubMed, Front Pharmacol) - "We derived an antibody specific normalized decrease of plasma p-tau181 (-15% for donanemab, -45% for aducanumab and -75% for lecanemab) to determine trial duration for achieving central amyloid negativity. This provides a hypothesis for the impact of disease pathology and gender effect on functional outcomes with lecanemab and gantenerumab. With further validation, this model has the capability to support optimization of clinical trial design for amyloid-tau combination therapy."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Dementia • p-tau181