Increased post-mitotic senescence in aged human neurons is a pathological feature of Alzheimer’s disease

Authors: Herdy JR, Traxler L, Agarwal RK, Karbacher L, Schlachetzki JCM, Boehnke L, Zangwill D, Galasko D, Glass CK, Mertens J, Gage FH

Cell Stem Cell, Volume 29, Issue 12 (2022)

Scientists use the noninvasive, label-free Maestro platform to investigate real-time electrical activity in vitro in an Alzheimer’s disease model.

Neuronal senescence has long been suspected as a feature of Alzheimer’s disease, but the underlying process is not fully understood. In this study, scientists model senescence in the Alzheimer’s brain in vitro using induced pluripotent stem cell-derived neurons and assess the impact of senotherapeutics. As part of the multiplatform experimental approach, the team used Axion’s noninvasive, label-free Maestro multielectrode array (MEA) system to demonstrate that Alzheimer’s disease neurons exhibit impaired electrical activity, which the authors suggest could play a role in the disruption in information processing in the brain. Other findings showed that the diseased neurons “present molecular and genetic markers of senescence and an inflammatory secretome that can trigger reactive astrogliosis.” Importantly, the scientists also demonstrated that senescence in neurons can be activated by oncogenes and eliminated with senolytic drugs—findings which could pave the way towards a novel therapeutic approach for slowing neuroinflammation and neurodegeneration in Alzheimer’s disease.