Amyloid Clearance and Transient CSF Aβ40 Reduction in a Case of ARIA-E/H Following Lecanemab Treatment
Yuki Naeshiro1, Fukiko Kitani-Morii1, Takashi Kasai1
1Department of Neurology, Graduate School of Medicine, Kyoto Prefectural University of Medicine, Japan.
Abstract:
We herein report a case of amyloid-related imaging abnormalities (ARIA)-E/H following lecanemab treatment in a 70-year-old man with mild cognitive impairment due to Alzheimer's disease. Generalized seizures occurred after the third infusion and were accompanied by fluid attenuated inversion recovery hyperintensity, microbleeds, and a minor acute infarct. Amyloid positron emission tomography revealed focal clearance of amyloid plaques in the ARIA-affected regions. CSF Aβ40 levels transiently decreased by about 30% during the ARIA episode, whereas Aβ42 remained stable, thereby increasing the Aβ42/40 ratio. These findings suggest that ARIA may facilitate focal amyloid clearance and that CSF Aβ40 reduction may serve as a potential biomarker for ARIA onset and resolution.
Insights
This case study shows amyloid-related imaging abnormalities (ARIA) may help clear amyloid plaques in Alzheimer's disease. Cerebrospinal fluid Aβ40 reduction may indicate ARIA onset and resolution.
Area of Science:
- Neurodegenerative diseases
- Alzheimer's disease therapeutics
- Biomarker discovery
Background:
- Lecanemab is an amyloid-targeting therapy for Alzheimer's disease.
- Amyloid-related imaging abnormalities (ARIA) are a known side effect of amyloid-targeting therapies.
- Understanding ARIA's impact on amyloid pathology is crucial for treatment optimization.
Purpose of the Study:
- To report a case of ARIA-E/H following lecanemab treatment.
- To investigate the relationship between ARIA and amyloid plaque clearance.
- To explore potential biomarkers for ARIA onset and resolution.
Main Methods:
- Case report of a 70-year-old male with mild cognitive impairment due to Alzheimer's disease.
- Clinical observation of generalized seizures post-lecanemab infusion.
- Neuroimaging (FLAIR, microbleeds, infarct) and Amyloid PET scans.
- Cerebrospinal fluid (CSF) analysis of amyloid-beta 40 (Aβ40) and Aβ42 levels.
Main Results:
- The patient developed ARIA-E/H with seizures, FLAIR hyperintensity, microbleeds, and acute infarct after lecanemab.
- Amyloid PET demonstrated focal amyloid plaque clearance in ARIA-affected areas.
- CSF Aβ40 levels decreased by ~30% during the ARIA episode, with a stable Aβ42 level, increasing the Aβ42/40 ratio.
Conclusions:
- ARIA may contribute to focal amyloid plaque clearance in Alzheimer's disease patients treated with lecanemab.
- Transient CSF Aβ40 reduction could serve as a potential biomarker for ARIA onset and resolution.
- Further research is warranted to validate these findings and their clinical implications.
