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Anti-Oligomer Antibodies for Alzheimer’s Disease

Editorialists provide insights into the role of brain oligomers in the development of early Alzheimer’s disease and a perspective on anti-oligomer monoclonal antibodies such as lecanemab. The op-ed piece relates to the results of lecanemab’s pivotal study. These are published in the current issue of the New England Journal of Medicine and were covered in PNN in late November when the research article was released in advance of publication.

“A downstream step in the progression of Alzheimer’s disease is accumulation of abnormally phosphorylated tau, and both amyloid and tau are currently being studied as imaging and body-fluid biomarkers that might predict the presence of pathologic processes in Alzheimer’s disease before the onset of clinical symptoms,” the editorialists write. “This observation raises the possibility that effective secondary-prevention strategies might spare these cognitively intact, biomarker-positive persons from the development of clinical dementia. Lecanemab or other oligomer-reducing interventions might be included in such a strategy. It is also likely that non-Aβ targets will be required to maximize benefits of treatment. Among these, glia and the immune–inflammatory system have attracted much recent attention, but we cannot yet say which molecules should be targeted, whether they should be activated or inhibited, or when during the disease we should target them. Thus, there remains much work ahead, but that should not distract from the achievement of the current trial in moving the needle on Alzheimer’s disease, however modestly.”

Source: New England Journal of Medicine