BioScience Trends. 2024;18(1):49-65. (DOI: 10.5582/bst.2023.01288)

Monoclonal antibody therapy for Alzheimer's disease focusing on intracerebral targets

Gu XL, Qi L, Qi Q, Zhou J, Chen S, Wang L

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Due to the complexity of the disorder and the presence of the blood-brain barrier (BBB), its drug discovery and development are facing enormous challenges, especially after several failures of monoclonal antibody (mAb) trials. Nevertheless, the Food and Drug Administration's approval of the mAb aducanumab has ushered in a new day. As we better understand the disease's pathogenesis and identify novel intracerebral therapeutic targets, antibody-based therapies have advanced over the past few years. The mAb drugs targeting β-amyloid or hyperphosphorylated tau protein are the focus of the current research. Massive neuronal loss and glial cell-mediated inflammation are also the vital pathological hallmarks of AD, signaling a new direction for research on mAb drugs. We have elucidated the mechanisms by which AD-specific mAbs cross the BBB to bind to targets. In order to investigate therapeutic approaches to treat AD, this review focuses on the promising mAbs targeting intracerebral dysfunction and related strategies to cross the BBB.

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