Dementia treatment with unknown effects and side effects... "Now you can detect it in advance with blood" [Health Check]

[Financial News] "How effective will it be for me, and how dangerous are the side effects?"
A clue has emerged to answer this question for patients and their families considering antibody treatment for Alzheimer's disease.
A research team led by Professor Kang Dong Woo of the Memory Disorder Clinic at the Department of Psychiatry, The Catholic University of Korea Seoul St. Mary's Hospital (first author Professor Ki-Hwan Byun) announced that it had found clues to assess treatment efficacy and the risk of side effects using immune protein levels in the blood measured before antibody therapy. The team confirmed that higher levels of complement component 1q were associated with a smaller reduction in amyloid, while lower levels of complement component 3 tended to be associated with more frequent amyloid-related imaging abnormalities (ARIA), a side effect.
Amyloid-targeting antibody therapy is a treatment that targets and helps remove amyloid beta accumulated in the brain. It is used for patients with confirmed brain amyloid accumulation at the mild cognitive impairment or mild dementia stage caused by Alzheimer's disease, with the goal of slowing the progression of cognitive decline. During treatment, cerebral edema and microhemorrhages may be detected on magnetic resonance imaging (MRI); these are referred to as amyloid-related imaging abnormalities (ARIA). It is important to identify risk factors before treatment and regularly perform MRI scans during treatment to monitor safety.
The research team retrospectively analyzed real-world clinical data from 62 patients with early-stage Alzheimer's disease who began Lecanemab treatment at The Catholic University of Korea Seoul St. Mary's Hospital. Among them, 34 patients who underwent amyloid positron emission tomography (PET) scans both before treatment and 26 weeks after treatment were also assessed for treatment-related changes in amyloid. In the PET follow-up group, the mean Centiloid value quantifying brain amyloid burden decreased from 67.8 before treatment to 38.1 after 26 weeks. The mean reduction was 29.7 Centiloids, or 43.8% of the pretreatment level.
Complement component 1q and complement component 3, examined by the research team, are part of the immune protein system known as complement. Complement is an auxiliary immune system that helps other immune cells eliminate bacteria, damaged cells, and abnormal proteins recognized in the blood and tissues. It marks targets for immune-cell processing and regulates inflammatory responses and elimination. Complement component 1q initiates the complement response, while complement component 3 plays a central role in the continuation of that response.
Although this remains a hypothesis based on preclinical and indirect clinical evidence, the academic community has reported the possibility that the complement pathway may be activated when anti-amyloid antibodies bind to amyloid beta inside and outside the brain. Based on this biological hypothesis, the research team analyzed the associations among pretreatment blood levels of complement component 1q and complement component 3, post-treatment amyloid reduction, and the occurrence of amyloid-related imaging abnormalities (ARIA).
The analysis found an association between higher pretreatment complement component 1q levels and a smaller reduction in amyloid measured by PET 26 weeks after treatment. The association remained in the same direction after accounting for age, sex, pretreatment amyloid burden, and apolipoprotein E ε4 (APOE ε4) carrier status. Conversely, amyloid-related imaging abnormalities (ARIA) were associated with greater frequency among patients with lower pretreatment complement component 3 levels. ARIA occurred in 7 of the 62 patients (11.3%); 5 cases were mild and 2 were moderate.
This was a single-center exploratory analysis, and only 7 of the 62 patients developed amyloid-related imaging abnormalities (ARIA), so further validation in large, multicenter studies is needed. Nevertheless, the study is considered meaningful because it identified an association between lower pretreatment complement component 3 levels and more frequent ARIA. Another feature of the study is that it examined treatment response and safety together by linking blood test data from real-world clinical practice with PET and MRI data.
If the findings are replicated in future multicenter prospective studies, complement component 1q and complement component 3 could become candidate biomarkers for pretreatment risk assessment alongside existing genetic information and brain imaging findings. This could help inform personalized treatment strategies that more precisely evaluate patient-specific differences in treatment response and safety using information that includes blood tests.
Professor Kang Dong Woo said, "The significance lies in confirming, by linking blood test and brain imaging data obtained in real-world clinical practice, that the complement proteins C1q and C3 may be associated with amyloid reduction and amyloid-related imaging abnormalities (ARIA), respectively, following anti-amyloid antibody therapy. We will verify their clinical utility through follow-up studies involving multiple institutions."
The Memory Disorder Clinic at the Department of Psychiatry at Seoul St. Mary's Hospital operates an integrated care system in collaboration with the Departments of Psychiatry, Neurology, Radiology, Nuclear Medicine, and Laboratory Medicine. The system links Alzheimer's disease diagnosis, amyloid PET and MRI assessment, genetic information testing, drug administration, and safety monitoring. This study was also conducted using data accumulated through these real-world clinical processes.
The findings were published in Alzheimer's & Dementia: Translational Research & Clinical Interventions (TRCI), an international journal published by the World Alzheimer's Association.



[email protected] Jeong Myeong-jin, Medical Specialist Reporter