The relation between family familiarity with autism and developmental outcomes.

Alzheimer’s disease (AD) represents a significant global challenge, particularly for the aging population. In the central nervous system (CNS), AD is characterized by extracellular amyloid-beta (Aβ) deposition, intracellular tau protein accumulation resulting in neurofibrillary tangles, and brain atrophy (DeTure and Dickson, 2019). Accompanying Aβ deposition and tau accumulation are innate immune system activation and neuroinflammation, both considered pathological hallmarks of AD. As the pivotal component of the innate immune system, microglia actively patrol the brain parenchyma and respond to phagocytose Aβ plaques (Yuan et al., 2016; Grubman et al., 2021; Teng et al., 2024). However, microglia gradually shift to a disease-associated state and promote chronic neuroinflammation (Leng and Edison, 2021). In addition to microglia, adaptive immune cells may also contribute to neurodegenerative diseases (Bettcher et al., 2021; Berriat et al., 2023). The role of adaptive immunity in AD is mostly linked to T cell populations, which can directly infiltrate the brain and exert either neuroprotective or deleterious roles in AD pathology (Baruch et al., 2015; Machhi et al., 2021; Chen et al., 2023; Jorfi et al., 2023; Su et al., 2023). However, very little is known about the role of lymphatic B cells in AD progression. Although there are several reports suggesting the potential implication of B cells in AD pathology, the percentage change of peripheral blood B cells in AD individuals and their correlation with disease severity are controversial (Richartz-Salzburger et al., 2007; Söllvander et al., 2015; Huang et al., 2022; Park et al., 2022; Wang et al., 2023). In addition, using immunodeficient mouse models of amyloid pathology, one study showed that depletion of mature B cells aggravated the Aβ load and memory deficits of mice with amyloid pathology (Marsh et al., 2016; Feng et al., 2023), whereas another study showed that B cell depletion reversed amyloid pathology (Kim et al., 2021). In particular, unlike the high numbers of T cell populations seen in the brain of AD individuals and mouse models of amyloid pathology, B lymphocytes are nearly absent in the CNS (Anthony et al., 2003; Ferretti et al., 2016; Croese et al., 2021; Jain and Yong, 2022), raising the critical question of how peripheral B cells are linked to amyloid pathology. Gamma-type immunoglobulin (IgG), produced by B lymphocytes, has diverse antigenic specificity in the adaptive immune system, but is also present in large amounts in blood without prior known antigenic experience, and is considered to be the first line of defense against pathogens, participating in the innate immune response (Panda and Ding, 2015; Akaishi and Misu, 2024; Li et al., 2024). IgG has been successfully used to clear Aβ aggregates both in AD animal models and patients (Sevigny et al., 2016; Dubey et al., 2020; McDade et al., 2022; Tanne, 2023). This suggests a potential interaction between blood-derived IgG and the cells within the CNS parenchyma. Currently, it remains unclear how IgG influences AD pathology. Thus, determining the localization pattern and function of IgG in AD brains will be of considerable significance for understanding the interaction between B cells and innate immune cells in AD pathology.