Alzheimer’s disease (AD) is a common neurodegenerative disease that currently has no known cure. Intravenous immunoglobulin (IVIG), which contains AD-related antibodies and has anti-inflammatory properties, has shown potential as a treatment for AD. However, the efficacy of clinical trials involving AD patients treated with IVIG has been inconsistent. Our previous study found that different IVIGs had significantly varied therapeutic effects on 3xTg-AD mice. In order to investigate the relationship between the composition and function of IVIG and its efficacy in treating AD, we selected three IVIGs that showed notable differences in therapeutic effects. Then, the concentrations of specific antibodies against β-amyloid (Aβ)₄₂, tau, and hyperphosphorylated tau (p-tau) in three IVIGs, as well as their effects on systemic inflammation induced by lipopolysaccharide (LPS) in Balb/c mice, were analyzed and compared in this study. The results indicated that these IVIGs differed greatly in anti-Aβ₄₂/tau antibody concentration and anti-p-tau ratio, and improved LPS-stimulated peripheral inflammation, liver and kidney injury, and neuroinflammation in Balb/c mice to varying degrees. Combined with our previous results, the efficacy of IVIG against AD may be positively correlated with its level of AD-related antibodies and anti-inflammatory ability. AD-related antibody analysis and functional evaluation of IVIG should be given sufficient attention before clinical trials, as this may greatly affect the therapeutic effect of AD treatment.

Intravenous immunoglobulin (IVIG) resistance occurs in 10–20% of children with Kawasaki disease (KD) and is associated with a 3- to 5-fold higher risk of coronary artery lesions (CALs). Yet the mechanistic basis for why some patients progress from reversible inflammation to irreversible vascular damage after IVIG remains poorly understood. Most existing reviews have focused on risk prediction rather than the mechanistic chain linking resistance to CALs. Here, we synthesize current evidence across three interconnected pathways. First, autophagy dysfunction—particularly impaired mitophagy—sustains inflammation through cGAS-STING activation. Second, neutrophil extracellular traps (NETs) play a controversial role in KD vasculitis, with PAD2 and PAD4 possibly acting redundantly via the NLRP3 inflammasome. Third, endothelial-to-mesenchymal transition (EndMT), driven by the IL-1β/TNF axis and the USP7-TGFβ2/SMAD pathway, emerges as a core event in vascular remodeling. Building on these findings, we propose the “autophagy–inflammasome axis” as a candidate molecular switch that dictates whether inflammation resolves or persists. This hypothesis is actionable: it generates three explicit, testable predictions linking autophagic integrity to inflammatory outcomes and therapeutic response. Direct experimental validation in IVIG-resistant KD models and patient samples is now urgently needed. This review provides a systematic framework for understanding how IVIG resistance transitions to irreversible CALs. It also identifies candidate biomarkers (e.g., S100A12, mtDNA, and MCM8) and therapeutic targets (autophagy inducers, NLRP3 inhibitors, USP7 inhibitors, and anakinra) that could enable earlier intervention.

Alzheimer’s disease (AD) is the most common cause of dementia worldwide and remains a major public health burden. Although amyloid-beta deposition and tau pathology are the defining pathological features of AD, increasing evidence indicates that immune dysregulation and chronic neuroinflammation also contribute to disease onset and progression. However, the specific immune pathways involved in AD and their mechanistic relevance remain incompletely understood. The major histocompatibility complex class I (MHC-I) antigen processing and presentation pathway has attracted growing attention because of its classical role in adaptive immunity and its potential functions within the central nervous system. In this narrative review, we summarize current evidence linking AD to the MHC-I, or human leukocyte antigen class I (HLA-I), pathway from genetic, molecular, cellular, and immunological perspectives. Available studies implicate the broader HLA region in AD susceptibility and suggest that alterations in HLA-I-related loci, antigen-processing machinery, MHC-I-associated molecules, and downstream immune responses may contribute to disease heterogeneity. At the molecular and cellular levels, changes in MHC-I molecules, antigen-processing machinery, and associated signaling pathways have been reported in microglia, neurons, astrocytes, and oligodendroglial lineage cells. In parallel, changes involving β ₂ -microglobulin and the presence of expanded or cytotoxic like CD8 ⁺ T cells suggest that adaptive immune mechanisms may participate in AD pathology. Nevertheless, direct evidence demonstrating immune responses specific to particular antigens and restricted by HLA-I in human AD remains limited. Overall, current findings indicate that the MHC-I/HLA-I pathway may represent an important component of AD pathophysiology and contribute to disease progression by influencing immune homeostasis and cellular interactions within the central nervous system. Further studies integrating human tissue analysis, immunopeptidomics, spatial profiling, and paired T cell receptor approaches are needed to clarify its mechanistic, biomarker, and therapeutic significance.

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease, and its pathogenesis is complex. In addition to amyloid-β and phosphorylated tau, inflammation and microbial infections also play a role in the development of AD. Currently, there is no effective clinical intervention to cure AD or completely halt its progression. Blood transfusion, a critical life-saving medical procedure widely employed in modern healthcare, faces growing demand due to global population aging. However, whether blood transfusion could increase the risk of AD is still not clear. Aβ and tau play major roles in the pathogenesis of AD and may possess the potential for transmission through blood transfusion. Iron overload and chronic inflammation, which can independently influence AD pathogenesis, may result from repeated transfusions. Additionally, herpesvirus, known to accelerate AD progression, can also be potentially transmitted by blood transfusion. In this study, recent advances in the associations between blood transfusion and the occurrence and development of AD were reviewed, and whether blood transfusion could increase the risk of AD was discussed. Furthermore, the related proposals for blood management and future research were advanced to provide references for the prevention and control of AD.

Background: As the most basic material, synthetic human Amyloid-β (1-42) (Aβ₄₂) peptide from different manufacturers have been widely used. Their aggregation ability is vital to the reliability, repeatability and comparability of studies on Aβ₄₂ physiology and pathology. However, it has not been evaluated and compared. Objective: To analyze the consistency of the aggregation ability of 5 commercially available Aβ₄₂ peptide. Methods: 5 Aβ₄₂ peptide represented as A, B, C, D and E were pretreated by HFIP. The pretreated Aβ₄₂ peptide were dissolved in Thioflavin T (ThT) solution, and their aggregation kinetics was monitored for 30 h with the aggregation kinetics test. Meanwhile, the pretreated peptide were aggregated in phosphate buffered saline. After aggregated for 12 h, they were detected by methods of ThT fluorescence, far-UV circular dichroism (CD), SDS-PAGE, western blot, and transmission electron microscopy (TEM), respectively. After aggregation for 8 h and 12 h, their cytotoxicity to SH-SY5Y cells was further evaluated using Cell Counting Kit-8. Results: For aggregation kinetics, peptide A, C and E remained low level curves, while peptide B and D presented typical sigmoidal kinetics curves. In CD measurement, the aggregates of peptide B and D showed relatively high negative CD peaks with the height of -8.09 mdeg and -14.37 mdeg, while the height of peptide A, C and E was -1.04, -3.55, and -3.88. In ThT assay, relative fluorescence intensity of the aggregates of peptide B and D were 7.79 and 8.82, higher than 1.19, 1.71, and 2.70 of peptide A, C and E, respectively. In SDS-PAGE, all aggregates contained monomers and eleven polymers. Moreover, peptide B-E presented a trapezoidal distribution from dimers to trimers, and peptide A aggregated to dimers. By western blot, the bands of monomers remained in all aggregates. Furthermore, peptide B and D aggregated to dimers and trimers, peptide A and C only aggregated to dimers, and peptide E showed a strong band of trimers. By TEM, protofibrils were observed only in peptide B, while substantial spherical aggregates were formed in other peptide. Additionally, peptide B, D and E exhibited higher cytotoxicity after aggregated for 8 h, whereas peptide A, B and D presented relatively high cytotoxicity after 12-hour aggregation. Conclusion: Commercially available Aβ₄₂ peptide showed obvious differences in aggregation ability, which should arouse enough attention in the field of basic study related to Aβ₄₂. The aggregation ability evaluation with the various assay methods has some discrepancies, and it is highly urgent to establish a reasonable and uniform measurement strategy.

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.