Mechanism of lecanemab in slowing Alzheimer's clarified
A collaborative research group led by Professor Kenjiro Ono of the Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, and Eisai Co., Ltd., used a newly developed measurement system for lecanemab-associated amyloid-β protofibrils (Lec-PF) to demonstrate that the concentration of Lec-PF in human cerebrospinal fluid is elevated in patients with Alzheimer's disease at all stages, from mild cognitive impairment to mild and severe dementia, compared with non-Alzheimer's disease controls
Furthermore, this research identified that the concentration of Lec-PF in cerebrospinal fluid is significantly correlated with biomarkers reflecting neurodegeneration. Lecanemab is a unique dual acting antibody that selectivity binds to amyloid-β protofibril (PF 2) in addition to removing plaque, and is a treatment for patients with mild cognitive impairment and mild dementia due to Alzheimer’s disease (AD 3) (collectively referred to as early AD). The results of this study suggest that PF which is captured by lecanemab (Lec-PF), is present in the cerebrospinal fluid of patients with Alzheimer’s disease, and that Lec-PF is a highly toxic pathological protein that causes neurodegeneration.
This research has revealed part of the mechanism by which lecanemab demonstrates its effect of slowing the progression of Alzheimer’s disease. Based on these findings, it may be possible in the future to measure Lec-PF concentration in cerebrospinal fluid before and after lecanemab treatment to assess the treatments efficacy. In addition, because the concentration of Lec-PF in cerebrospinal fluid correlates well with neurodegenerative markers such as total tau and neurogranin, it is expected that these findings could also be useful in predicting the prognosis of Alzheimer’s disease patients.
Future Developments Measuring the Lec-PF concentration in CSF before and after lecanemab treatment may be useful in assessing the efficacy of lecanemab treatment. In addition, because the concentration of Lec-PF in CSF correlates well with neurodegenerative markers, it may also be useful for predicting the prognosis of AD patients.
This research was published in the online version of the international academic journal Annals of Neurology at 18:30 on January 6, 2025 (US Eastern Standard Time).
Citation: "Lecanemab-associated amyloid-β protofibril in cerebrospinal fluid correlates with biomarkers of neurodegeneration in Alzheimer’s disease (Cerebrospinal fluid (CSF) lecanemab-associated amyloid protofibril concentrations correlate well with neurodegenerative biomarkers in AD)". Authors: Moeko Noguchi-Shinohara, Kazuyoshi Shuta, Hidetomo Murakami, Yukiko Mori, Junji Komatsu, Chizuru Kobayashi, Steven Hersch, Kanta Horie, Kenjiro Ono (Moeko Shinohara, Kazuyoshi Shuta, Hidetomo Murakami, Yukiko Mori, Junji Komatsu, Chizuru Kobayashi, Steven Hersch, Kanta Horie, Kenjiro Ono) Date of publication: January 6, 2025.
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