ArticleAnnals of neurology2025
Lecanemab-Associated Amyloid-β Protofibril in Cerebrospinal Fluid Correlates with Biomarkers of Neurodegeneration in Alzheimer's Disease.
Article in Annals of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed.
- Real-world long-term continuation of lecanemab therapy and the clinical utility of phosphorylated tau 181.The journal of prevention of Alzheimer's disease · 2026Article
- Immunotherapy with B28, an antibody to Aβ oligomers, potently decreases amyloid plaques, microgliosis, and memory decline in APP knock-in mice.Cell reports · 2026Article
- Molecular Dynamics Simulations of AβACS omega · 2026Article
- Antiamyloid Antibody Effects on Aβ-42 Protein Aggregates Profiled Using Nanospectroscopy.Chemical & biomedical imaging · 2026Article
- Endogenously generated Dutch-type Aβ non-fibrillar aggregates dysregulate presynaptic neurotransmission in the absence of detectable inflammation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Novel Monoclonal Antibody Detects Small Aβ Oligomers More Sensitively Than Lecanemab in Alzheimer's Disease CSF, Serum and Culture Media.Annals of neurology · 2026Article
- Article
- Targeting protein aggregate co-pathologies in neurodegeneration: a viable therapeutic strategy?Molecular neurodegeneration advances · 2026Review
- Amyloid Beta in Alzheimer's Disease: Mechanisms, Biomarker Potential, and Therapeutic Targets.CNS neuroscience & therapeutics · 2025Review
- Higher phosphorylated tau levels predict cognitive decline and amyloid-related imaging abnormalities during lecanemab treatment: clinical practice data.Alzheimer's research & therapy · 2025Article
- Lecanemab treatment for Alzheimer's Disease of varying severities and associated plasma biomarkers monitoring: A multi-center real-world study in China.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- A manifesto for Alzheimer's disease drug discovery in the era of disease-modifying therapies.Molecular neurodegeneration · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
objectiveThe Clarity AD phase III trial showed that lecanemab reduced amyloid markers in early Alzheimer's disease (AD) and resulted in less decline on measures of cognition and function than placebo. Herein, we aimed to characterize amyloid-β (Aβ) protofibril (PF) captured by lecanemab in human cerebrospinal fluid (CSF) from living participants with different stages in AD, which enable an enhanced understanding of the dynamic changes of lecanemab-associated Aβ-PF (Lec-PF) in vivo.
methodsWe newly developed a unique and highly sensitive immunoassay method using lecanemab that selectively captures Lec-PF. The CSF level of Lec-PF, Aβ42, Aβ40, p-tau181, p-tau 217, total tau, and neurogranin were measured in Japanese participants (n = 163). The participants in this study consisted of 48 cognitively unimpaired Aβ-negative (CU-), 8 cognitively impaired diagnosed as suspected non-Alzheimer's disease pathophysiology, 9 cognitively unimpaired Aβ-positive (CU+), 34 Aβ-positive with mild cognitive impairment (MCI+), and 64 Aβ-positive with AD dementia (AD+).
resultsThe CSF Lec-PF levels significantly increased in the groups of MCI+ and AD+ compared with CU- group. Notably, CSF Lec-PF showed modest correlation with plaque-associated biomarkers in Aβ-positive participants and stronger correlation with neurodegeneration biomarkers, such as CSF total tau and neurogranin, suggesting that CSF Lec-PF levels proximally reflect neurodegeneration as well as the amount of senile amyloid plaques.
interpretationThis is the first report describing Aβ-PF species captured by lecanemab in human CSF and supporting that Lec-PF is correlated with neurodegeneration in AD and may explain the mechanism of the clinical effect of lecanemab. ANN NEUROL 2025;97:993-1006.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.