阿尔茨海默症治疗的药物突破
摘要
<p indent="0mm">Alzheimer’s disease (AD) is the most common neurodegenerative disorder that mainly affects elderly people. AD is a progressive disease beginning with mild learning and memory impairment and gradually evolving to severe dementia, which is accompanied by impairments in complex attention, language function, behavior, and social ability. Two primary neuropathological hallmarks in the brain of AD patients have been recognized and studied extensively, including the accumulation of extracellular plaques primarily comprising aggregated amyloid-β (Aβ) and intracellular neurofibrillary tangles (NFTs) constituted of hyperphosphorylated Tau protein. As the population aging intensifies, the incidence of AD increases accordingly. Thus, there is an urgent need to develop effective therapies to prevent or slow down the progression of AD. Although many drugs have been designed to target AD pathology, only a few have entered the clinical trials, mainly monoclonal antibodies targeting Aβ. The goal of many anti-Aβ antibodies is to lower the levels of parenchymal Aβ as well as Aβ deposition in the AD brain. The amyloid cascade hypothesis suggests that Aβ accumulation triggers disease pathogenesis, so therapies that lower parenchymal Aβ might be expected to slow AD progression. Recently, the U.S. Food and Drug Administration (FDA) has approved Lecanemab and Donanemab, both are anti-Aβ monoclonal antibodies that target and remove Aβ from the brain, for the treatment of AD. Among AD patients with the early symptom, Lecanemab and Donanemab could effectively reduce Aβ deposition and are proven to be clinically meaningful benefits based on clinical rating scales such as CDR-SB and iADRS. These findings support that Aβ indeed is an effective therapeutic target.Besides having serious adverse events, such as microhemorrhage, superficial siderosis (ARIA-H), and amyloid-related imaging abnormalities (ARIA) with edema or effusions (ARIA-E),these antibody-based regimes appear to be e