[Sportschosun, Reporter Jang Jong-ho] Patients and families considering antibody treatment for Alzheimer’s disease are primarily concerned about two things.
The questions are, "How effective will it be for me?" and "How dangerous will the side effects be?" To find clues to these questions, a research team from the Department of Psychiatry at The Catholic University of Korea, Seoul St. Mary’s Hospital recently published findings based on blood tests and brain imaging from patients who actually received the treatment.
A research team led by Professor Kang Dong-woo of the Memory Disorders Clinic in the Department of Psychiatry at The Catholic University of Korea, Seoul St. Mary’s Hospital, with Professor Byun Ki-hwan as first author, said it had found clues for estimating treatment efficacy and the risk of side effects based on pretreatment levels of immune proteins in the blood. The study found that higher levels of the complement protein C1q were associated with less amyloid reduction, while lower C3 levels were associated with a higher frequency of amyloid-related imaging abnormalities (ARIA), a treatment-related side effect.
Antibody treatment targeting amyloid proteins is designed to help remove amyloid beta accumulated in the brain. It is used for patients with confirmed brain amyloid accumulation who have mild cognitive impairment or mild dementia caused by Alzheimer’s disease, with the goal of slowing the progression of cognitive decline. During treatment, brain swelling and microbleeds may be detected on magnetic resonance imaging (MRI); these findings are known as ARIA. Therefore, identifying risk factors before treatment and conducting regular MRI scans during treatment are important for monitoring safety.
The research team retrospectively analyzed real-world clinical data from 62 patients with early Alzheimer’s disease who began lecanemab treatment at The Catholic University of Korea, Seoul St. Mary’s Hospital. Among them, 34 patients underwent amyloid positron emission tomography (PET) scans both before treatment and 26 weeks after treatment, allowing the researchers to examine treatment-related changes in amyloid levels. In this PET follow-up group, the mean Centiloid value, which quantifies the brain’s amyloid burden, fell 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.
C1q and C3 are components of the immune protein system known as the complement system. Complement acts as a kind of immune-support system in the blood and tissues, helping other immune cells remove bacteria, damaged cells, and abnormal proteins when they are recognized. It marks targets for immune-cell clearance and regulates inflammatory responses and the removal process. C1q initiates the complement response, while C3 plays a central role as that response continues.
Although this remains a hypothesis based on preclinical and indirect clinical evidence, studies have suggested 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 between pretreatment blood levels of C1q and C3, subsequent amyloid reduction, and the occurrence of ARIA.
The analysis showed an association between higher pretreatment C1q levels and a smaller reduction in amyloid on PET scans performed 26 weeks after treatment. The same direction of association was observed after accounting for age, sex, pretreatment amyloid burden, and apolipoprotein E ε4 (APOE ε4) carrier status. By contrast, ARIA was observed more frequently in patients with lower pretreatment C3 levels. Among all 62 patients, ARIA occurred in seven, or 11.3%; five cases were mild and two were moderate.
Because this was a single-center exploratory analysis involving only seven patients who developed ARIA among the 62 participants, the findings require further validation in large, multicenter studies. Nevertheless, the study is considered meaningful because it identified an association between lower pretreatment C3 levels and a higher frequency of ARIA. Another notable feature was that it examined treatment response and safety together by linking blood tests with PET and MRI data obtained in routine clinical care.
If the findings are replicated in future multicenter prospective studies, C1q and C3 could become candidate biomarkers for pretreatment risk assessment, alongside existing genetic information and brain-imaging findings. This could help advance personalized treatment strategies that use blood-test data and other information to assess differences in treatment response and safety more precisely for individual patients.
Professor Kang Dong-woo, who led the study, said, "The significance of this study lies in linking blood-test and brain-imaging data obtained in actual clinical practice and identifying the possibility that the complement proteins C1q and C3 are respectively associated with amyloid reduction and ARIA during anti-amyloid antibody treatment." He added, "We will verify their clinical usefulness through follow-up studies involving multiple institutions."
The findings were recently published in Alzheimer's & Dementia: Translational Research & Clinical Interventions (TRCI), an international academic journal published by the World Alzheimer’s Association.
Jang Jong-ho, Reporter — bellho@sportschosun.com
This article has been translated by GripLabs Mingo AI.
