Alzheimer's Disease and the Immune System: A Comprehensive Overview With a Focus on B Cells, Humoral Immunity, and Immunotherapy Publisher



Gol Mohammad Pour Afrakoti L ; Daneshpour Moghadam S ; Hadinezhad P
Source: Journal of Alzheimer's Disease Reports Published:2025

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder and the major cause of dementia. Amyloid-β (Aβ) and tau aggregation, mitochondrial dysfunction, and microglial dysregulation are key contributors to AD pathogenesis. Impairments in the blood-brain barrier have unveiled the contribution of the immune system, particularly B cells, in AD pathology. B cells, a crucial component of adaptive immunity, exhibit diverse functions, including antigen presentation and antibody production. While their role in neuroinflammatory disorders has been well-documented, their specific function in AD lacks adequate data. This review examines the dual role of the B cells and humoral immunity in modulating brain inflammation in AD and explores recent advancements in passive and active immunotherapeutic strategies targeting AD pathobiology. We summarize preclinical and clinical studies investigating B cell frequency, altered antibody levels, and their implications in neuroinflammation and immunotherapy. Notably, B cells demonstrate protective and pathological roles in AD, influencing neurodegeneration through antibody-mediated clearance of toxic aggregates and inflammatory activation inflammation. Passive immunotherapies targeting Aβ have shown potential in reducing amyloid plaques, while active immunotherapies are emerging as promising strategies, requiring further validation. Understanding the interplay between B cells, humoral immunity, microglia, and mitochondrial dysfunction is critical to unraveling AD pathogenesis. Their dual nature in disease progression underscores the need for precise therapeutic interventions to optimize immunotherapy outcomes and mitigate neuroinflammation effectively. © The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).