Seeding the problem

Abstract

Neurodegeneration A key pathological event in Alzheimer's disease (AD) is the aggregation and deposition of amyloid-β (Aβ). However, the formation of Aβ deposits is a relatively late readout of the Aβ aggregation process. Treatments that affect such deposits may fail to interrupt the critical early seeding stage of Aβ deposition. It remains unclear when pathogenic Aβ seeds begin to form, propagate, and spread through the brain. Furthermore, the precise nature of the initial Aβ seeds remains unknown. Working in mouse models of AD, Uhlmann et al. tested a variety of known antibodies for their ability to neutralize Aβ seeds before amyloid deposition was detectable. Early administration of one such antibody, aducanumab, significantly reduced Aβ deposition and the resulting pathology. This work points to targeting and removal of early Aβ seeds as promising future therapies for patients developing AD. Nat. Neurosci. 10.1038/s41593-020-00737-w (2020).