Is there a role for B cells in Alzheimer's disease?

Résumé fourni par la source

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder associated with dementia, progressive neuronal loss, extracellular amyloid-β (Aβ) and intracellular hyperphosphorylated tau deposition. Currently, no curative therapies are available for this condition. Beyond these features, AD pathogenesis is associated with neuroinflammation, which is thought to be primarily driven by microglial cells, and has evolved as an important contributor to AD pathogenesis over the past decade. Although microglia cells play a central role in neuroinflammation, they are also a highly heterogeneous population existing in distinct transcriptional states that can be either beneficial or detrimental to disease progression. Importantly, microglial activation and the ensuing neuroinflammatory milieu do not operate independently of the systemic immune system. The longstanding view of the brain as an immune-privileged organ has been fundamentally revised, with increasing evidence demonstrating that the crosstalk between brain-resident and circulating peripheral immune cells plays a pivotal role in AD pathogenesis. Peripheral immune cells, recruited in the central nervous system in response to Aβ and tau pathology, actively modulate the neuroinflammatory environment. While CD4 + and CD8 + T cells have been extensively investigated in this context, the contribution of B cells to AD remains poorly understood. Here, we comprehensively review the phenotypic and functional alterations of B cells in AD, integrating evidence from experimental models and human studies, to evaluate whether B cells constitute an underappreciated component of the adaptive immune response in AD and whether they represent a compelling immunotherapeutic target. We also highlight key unresolved questions and propose future research directions to guide the field towards a deeper mechanistic understanding of B cell biology in AD.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.