A microglia-containing 3D human brain organoid for studying HSV-1-induced Alzheimer’s disease

Abstract

Alzheimer’s disease (AD), recognized for its profound incapacitation, presents with notable cognitive decline and memory deficits. A growing body of research points to a link between infection with herpes simplex virus type 1 (HSV-1) and the exacerbation of AD. Our study pioneers the use of a cutting-edge, three-dimensional human brain organoid model enriched with microglia, referred to as MC-HBO, to explore the mechanisms by which HSV-1 influences the pathogenesis of AD. Through this model, we examined the regulatory effects of cytokines on amyloid-β (Aβ) deposition, a cardinal pathological manifestation of AD. Our findings demonstrate that the suppression of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), leads to a significant reduction in Aβ deposition. In contrast, the inhibition of anti-inflammatory cytokines, such as interleukin-10 (IL-10) and interleukin-4 (IL-4), was correlated with an increase in Aβ accumulation. These insights into the role of cytokine signaling pathways suggest a promising therapeutic strategy for potentially decelerating the progression of AD.