Aduhelm (aducanumab) / Neurimmune, Eisai - LARVOL DELTA

"Unveiling Alzheimer's Disease (1901-2025): Historical Insights, Global Burden, Biological Mechanisms, Diagnostics, And Therapeutic Strategies". (PubMed, Ageing Res Rev) - "Therapeutically, the landscape has shifted from symptomatic treatments (e.g., cholinesterase inhibitors, memantine) to disease-modifying agents. Recent FDA approvals of monoclonal antibodies like Aducanumab, Lecanemab, and Donanemab mark a new era in targeted immunotherapy...Emerging drug delivery systems, including nanocarriers and intranasal formulations, aim to overcome the BBB and enhance therapeutic efficacy. The manuscript emphasizes the urgent need for integrative, personalized, and scalable solutions to manage AD's growing burden."

IO biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Mental Retardation • Psychiatry

Severe symptomatic amyloid-related imaging abnormalities in Alzheimer's disease: Two case reports and systematic review of reported cases. (PubMed, J Alzheimers Dis) - "Fifteen cases were associated with lecanemab, 10 with gantenerumab, 6 with donanemab, and 5 with other antibodies...Standardized diagnostic and therapeutic guidelines are needed to minimize ARIA-related morbidity and mortality.PROSPERO registration no. CRD420251055067."

Journal • Review • Alzheimer's Disease • CNS Disorders • Epilepsy • Hematological Disorders • Pain • APOE

Amyloid Beta in Alzheimer's Disease: Mechanisms, Biomarker Potential, and Therapeutic Targets. (PubMed, CNS Neurosci Ther) - "Incorporating new research findings and ongoing debates surrounding the Aβ cascade hypothesis is crucial for improving early diagnosis and for guiding the development of effective treatments for AD."

Biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • Metabolic Disorders • APP

Rapidly Progressive Dementia: Predictive Clues and a Proposed Diagnostic Approach Focused on Neurodegenerative Causes. (PubMed, Cureus) - "Conclusion Considering these factors, ND disorders-historically viewed as diagnoses of exclusion-may become a central component of the diagnostic approach to RPD, alongside autoimmune encephalitis (AE). We propose the development of an algorithm based on a predictive model that allows for the identification of a subgroup of patients in whom the diagnostic approach can be optimized, avoiding unnecessary studies and prioritizing the early identification of a possible ND etiology."

Journal • CNS Disorders • Dementia • Immunology

Hippocampal Atrophy on Magnetic Resonance Imaging as a Surrogate Marker for Clinical Benefit and Neurodegeneration in Early Symptomatic Alzheimer's Disease: Synthesis of Evidence from Observational and Interventional Trials. (PubMed, CNS Drugs) - "These trials included four amyloid antibodies (aducanumab, lecanemab, donanemab, and gantenerumab) and one oral anti-oligomer agent (valiltramiprosate). HV on standardized vMRI is sensitive to anti-amyloid treatments, demonstrating strong correlations between slowed hippocampal atrophy and slowed cognitive decline. Data from over 23,000 subjects over three decades support HV as a surrogate marker for predicting clinical benefit in early symptomatic AD."

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

Modeling amyloid plaque turnover dynamics improves characterization of drug effects. (PubMed, Alzheimers Dement (N Y)) - "The model provides a fundamental measure of drug effects on plaque, independent of disease stage and study-design factors, improving cross-study comparisons and enabling predictions."

Journal • Alzheimer's Disease • CNS Disorders

Evaluating amyloid-beta as a surrogate endpoint in trials of anti-amyloid-beta drugs in Alzheimer's disease: a Bayesian meta-analysis. (PubMed, J Comp Eff Res) - " Although our results from the analysis of data across all MABs suggested that Aβ was a potential surrogate endpoint for CDR-SOB, individually the surrogacy patterns varied across treatments and showed no evidence of association. Bayesian information-sharing revealed moderate surrogate relationship only for aducanumab and lecanemab."

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

Relationship between efficacy and preferential targeting of soluble Aβ aggregates. (PubMed, Alzheimers Dement (N Y)) - "These results suggest that selectivity for soluble toxic oligomers correlates with clinical efficacy, potentially attenuating monomer competition and amyloid-related imaging abnormalities (ARIA)."

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

Comparative efficacy and safety of symptomatic therapy and disease-modifying therapy for Alzheimer's disease: a systematic review and network meta-analysis. (PubMed, Front Neurosci) - "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%)...Lecanemab provides moderate benefits, while donanemab appears less effective. Thus, clinicians should apply disease-modifying therapies cautiously and individually, carefully balancing potential risks and benefits for each patient. PROSPERO [CRD42025637730], https://www.crd.york.ac.uk/PROSPERO/."

Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry

Microglial lipid droplets as therapeutic targets in age-related neurodegenerative diseases. (PubMed, NPJ Aging) - "Monoclonal antibodies approved for Alzheimer's disease (AD), such as lecanemab and aducanumab, have been shown to enhance microglial phagocytic function, underscoring the therapeutic relevance of microglia in neurodegenerative diseases (NDDs). We further propose a hypothetical mechanism by which LDs clearance restore energy metabolism, nuclear transport, facilitate DNA repair, suppress inflammation, and phagocytosis in microglia. Thus, elucidating LDs dynamics in microglia may provide novel therapeutic avenues for modifying the course of NDDs."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • Metabolic Disorders

Targeting Amyloid-β Proteins as Potential Alzheimer's Disease Therapeutics: Anti-Amyloid Drug Discovery, Emerging Therapeutics, Clinical Trials and Implications for Public Health. (PubMed, Pharmaceuticals (Basel)) - "We have evaluated the most recent developments in monoclonal antibodies, including aducanumab (discontinued November 2024), lecanemab, and donanemab, emerging therapeutic options, as well as emerging strategies such as tau-targeting therapies, gene therapy, and small molecule inhibitors. Moreover, we highlighted the challenges and opportunities in AD research, including the need for early diagnosis, personalized medicine, and combination therapies. Our review will offer a concise and informative overview of the current landscape and future directions in anti-Aβ therapeutics for AD, shedding light on potential treatments and prospects for improving patient outcomes."

Journal • Review • Alzheimer's Disease • CNS Disorders • Gene Therapies

Nanomedicine Solutions for Alzheimer's Disease: A Critical Review of Therapeutic Nanoparticle Strategies. (PubMed, ACS Omega) - "The recent approval of aducanumab, an antibody clearing amyloid beta plaques, brings hope, though its therapeutic benefits are controversial...Despite extensive research, only a small fraction of these studies progress to clinical trials. Continuous nanomedicine research is poised to play a vital role in future AD management, providing innovative solutions to this devastating disease."

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

Aducanumab Binding to Aβ1-42 Fibrils Alters Dynamics of the N-Terminal Tail While Preserving the Fibril Core. (PubMed, bioRxiv) - "This interaction, which spans D1 to S8 and extends to Y10 on the fibril surface, is consistent with a mechanism in which N-terminal binding by the antibody interferes with aggregation steps like secondary nucleation. These findings detail how aducanumab engages its target fibril and provides insights relevant to other clinically approved antibodies and next-generation therapies that recognize the Aβ N-terminal region."

Journal • Alzheimer's Disease • CNS Disorders

Effect of Alzheimer's disease medications on neurocognitive outcomes in children and adolescents with autism spectrum disorder and low IQ: a scoping review. (PubMed, Transl Psychiatry) - "This scoping review identified promising evidence of neurocognitive improvement in children and adolescents with ASD and low IQ following treatment with either a cholinesterase inhibitor or an NMDA receptor antagonist. Considering the lack of FDA-approved treatments for the cognitive deficits associated with ASD and an absence of medications approved to treat core features of ASD, our findings highlight an opportunity for innovative directions in autism research and treatment."

Journal • Review • Alzheimer's Disease • Autism Spectrum Disorder • CNS Disorders • Cognitive Disorders • Developmental Disorders • Genetic Disorders • Mental Retardation

Network Controllability Reveals Key Mitigation Points for Tumor-Promoting Signaling in Tumor-Educated Platelets. (PubMed, Int J Mol Sci) - "A low-dose combination therapy of fostamatinib, Aducanumab, and acetylsalicylic acid (aspirin) may control TEP effects. In conclusion, our preclinical in silico approach revealed FDA-approved drugs that allow therapeutic targeting of metastasis-promoting TEPs and target NSCLC at the same time."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FCGR2A • ITGA2B • SYK

Detection of extracellular amyloid beta aggregates by an Aducanumab-based synNotch receptor: an in vitro proof-of-concept study. (PubMed, J Transl Med) - "These findings establish that synNotch receptors can be engineered to detect and respond to pathological extracellular protein aggregates such as Aβ. This expands the scope of synNotch-based systems and supports their potential for developing precision cell-based therapies for neurodegenerative diseases like AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Oncology

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) - "Grant Support NIH Grant R01 NS119593; Grant Support 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

Variations in Screening and Medication Takeup Rates for Alzheimer's Disease (ISPOR-EU 2025) - "Medications include Cholinesterase Inhibitors , 2) Memantine 3) and three newer immunotherapy drugs (Lecanemab, Aducanumab, Donanemab). Successful adoption of AD medications will require substantial practice changes, including an increased use of imaging and an increased proportion of persons with AD being diagnosed in an early disease stage. High variation in screening/medication rates suggest opportunities to improve overall care."

Alzheimer's Disease • CNS Disorders

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