# Can IVIG Intervene in AD? Insights from Animal Experiments and Clinical Trials—A Systematic Review and Synthesis Without Meta-Analysis

## TL;DR

This paper reviews studies on using IVIG for Alzheimer's disease, showing it's safe and may help with cognitive decline, but results vary.

## Contribution

The study systematically reviews animal and clinical data on IVIG for AD, highlighting its safety and potential peripheral clearance mechanism.

## Key findings

- IVIG treatment delayed cognitive degradation in AD mice and patients.
- Aβ and tau levels increased in plasma but decreased in the brain or CSF, suggesting a peripheral clearance mechanism.
- IVIG combined with plasma exchange improved language, memory, and praxis in AD patients.

## Abstract

The clinical safety of intravenous immunoglobulin (IVIG) is well-established, offering potential as a “one-drug, multi-target” intervention for Alzheimer’s disease (AD). However, its efficacy remains inconclusive and appears closely related to specific functional properties. Therefore, we conducted a systematic review based on the analysis of prior animal and clinical trials to provide insights for future IVIG-based therapeutic development. A systematic search was conducted across PubMed, Embase, the Cochrane Library, Web of Science, PsycInfo, ClinicalTrials.gov, SinoMed, and Wanfang databases for the relevant literature published up to 30 October 2025, using terms related to Alzheimer’s, IVIG, and β-amyloid protein. Consequently, IVIG demonstrated clinical safety, though methodologies—including dosages, models, and manufacturers—varied significantly across studies. In most cases, IVIG treatment delayed cognitive degradation in both AD mice and patients. Biologically, Aβ and tau levels increased in plasma while decreasing in the brain or cerebrospinal fluid (CSF), suggesting a peripheral clearance mechanism distinct from that of monoclonal antibody interventions. Additionally, brain atrophy was alleviated, and pathological plaques were reduced. In the context of plasma exchange (PE) combination therapy, the administration of IVIG further contributed to improvements in language, memory, and praxis. IVIG possesses a favorable safety profile and can ameliorate AD symptoms, yet efficacy varies considerably between trials. To advance treatment, future research should investigate the reasons for these variances and establish a standardized system for evaluating preclinical IVIG interventions, thereby facilitating the development of specific IVIG products for AD.