Host immune response genes and amyloid-beta pathway components

The Host immune response genes and amyloid-beta pathway components represent a complex biological network central to the pathogenesis of Alzheimer's disease. The amyloid-beta (Aβ) pathway involves the sequential proteolytic cleavage of amyloid precursor protein (APP) by enzymes such as BACE1 and gamma-secretase, leading to the accumulation of neurotoxic Aβ peptides and the formation of extracellular plaques [1][3]. Concurrently, host immune response genes, particularly those expressed in microglia such as TREM2, CD33, and CR1, regulate the brain's innate immune response to these aggregates, influencing plaque clearance and the degree of neuroinflammation [2]. Therapeutic strategies targeting this system include anti-amyloid monoclonal antibodies designed to clear existing plaques and small molecules aimed at inhibiting Aβ production or modulating microglial activity [4]. However, drug development in this area faces significant challenges, including the risk of Amyloid-Related Imaging Abnormalities (ARIA) and the requirement for intervention early in the disease course before irreversible neurodegeneration occurs [1][4]. This target group highlights the critical intersection between protein misfolding and innate immunity in neurodegenerative pathology. [1] Karran, E., & De Strooper, B. (2022). Nature Reviews Drug Discovery. [2] Deczkowska, A., et al. (2020). Cell. [3] Haass, C., & Selkoe, D. J. (2007). Nature Reviews Molecular Cell Biology. [4] FDA (2023). Leqembi Prescribing Information.

Other names

Alzheimer's disease neuroinflammation and amyloidogenic pathwaysAβ-immune axisAmyloid-beta and neuroimmune signalingMicroglial immune response and APP processing pathway

Amyloid-beta clearance via monoclonal antibodies; inhibition of beta-secretase (BACE1) or gamma-secretase to reduce Aβ production; modulation of microglial phagocytic activity through TREM2 or CD33 signaling.