Alzheimer’s disease (AD) is a complex neurodegenerative disorder driven jointly by immune imbalance, protein aggregation, and metabolic dysregulation. Emerging evidence indicates that its pathological progression is not confined to amyloid-β (Aβ) accumulation or tau hyperphosphorylation, but rather reflects a network-level dysregulation between central and peripheral immune systems. Immunotherapeutic strategies have advanced considerably, including passive and active approaches targeting Aβ (e.g., aducanumab and lecanemab) and tau (e.g., gosuranemab), as well as modulators of microglial function and systemic immunity (e.g., AL002, XPro1595, masitinib, sargramostim, and baricitinib). Additionally, interventions targeting the gut–brain axis (e.g., sodium oligomannate, probiotics, and prebiotics) and metabolic regulators (e.g., semaglutide) expand the immunomodulatory landscape. However, translating such changes into sustained and clinically meaningful cognitive benefits remains constrained by disease heterogeneity, intervention timing, intracellular target accessibility, and safety-tolerability considerations. Future work should emphasize precise stratification, early intervention, artificial intelligence (AI)-enabled analytics, and multimodal biomarker guidance, while advancing central nervous system-penetrant and safer therapeutic and delivery strategies. Collectively, AD immunotherapy is undergoing a paradigm shift from “pathology clearance” to “immune network restoration,” aiming to achieve durable disease modification through multidimensional and systemically coordinated interventions.
Background: The neuropathological diagnosis in post-mortem human brain is the golden standard and crucial for achieving the ultimate goal of serving brain research via human brain banking. With the construction of a China brain bank network, it is urgent to establish a unified protocol, including standardized neuropathological staining protocols, to ensure identical and reliable diagnostic results across different brain banks and to enable future sample sharing for research.
Method: This study focused on optimizing immunohistochemical (IHC) staining protocols for four key neuropathological markers of neurodegenerative diseases: hyperphosphorylated Tau protein, β-amyloid, α-synuclein, and phosphorylated transactive response DNA-binding protein 43. The optimization was performed on formalin-fixed, paraffin-embedded human brain tissues by modifying conditions including antigen retrieval. The optimized stainings were compared with those from the highly standardized Netherlands Brain Bank.
Results: Through protocol optimization and comparison with the Netherlands Brain Bank standards, we obtained optimal and consistent staining results suitable for reliable neuropathological diagnosis.
Discussion: This study provides a solid foundation for quality control of IHC staining and for accurate neuropathological diagnosis within the framework of China brain banking.
Background: China urgently requires a standardized operational protocol for its fetal brain tissue bank. The establishment of such a protocol is essential to address gaps in the current domestic standardized framework, enhance both basic research and clinical studies, and address ethical and sample quality challenges.
Materials and methods: By leveraging the practical insights from several domestic brain banks, this protocol defines the goals of fetal brain tissue collection, establishes the legal and ethical foundations for such collection, specifies the range of clinical data to be gathered and the procedures for sampling fetal brain tissue, briefly outlines the standards for pathological diagnosis, details the preservation and management of fetal brain tissue-related information, and explains the principles governing applications for fetal brain tissue use.
Results: This protocol provides unified and standardized benchmarks, and strengthens the entire chain of sample collection, processing, and sharing for the establishment of a fetal brain tissue bank.
Conclusion: By providing a comprehensive framework, this protocol ensures operational consistency and minimizes experimental bias, thereby facilitating reproducible and comparable research outcomes across institutions. This standardized operational protocol will advance brain science research by ensuring the availability of high-integrity fetal brain tissue samples, ultimately enhancing China’s competitiveness in the international neuroscience community.