High molecular weight amyloid β 1‐42 oligomers induce neurotoxicity via plasma membrane damage

• DOI: 10.1096/fj.201900604r
• Publication Date: 2019-05-14T00:20:22Z
• Authors: Taro Yasumoto; Yusaku Takamura; Mayumi Tsuji; Takahiro Watanabe...; Keiko Imamura; Haruhisa Inoue; Shiro Nakamura; Tomio Inoue; Atsushi Kimura; Satoshi Yano; Hisao Nishijo; Yuji Kiuchi; David B. Teplow; Kenjiro Ono
• Keywords: Neurotoxicity; Amyloid (mycology)

Amyloid β-protein (Aβ) molecules tend to aggregate and subsequently form low MW (LMW) oligomers, high (HMW) aggregates such as protofibrils, ultimately fibrils. These Aβ species can generally amyloid plaques implicated in the neurodegeneration of Alzheimer disease (AD), but therapies designed reduce plaque load have not demonstrated clinical efficacy. Recent evidence implicates oligomers AD neuropathology, precise mechanisms are uncertain. We examined neuronal dysfunction from HMW-Aβ1-42 exposure by measuring membrane integrity, reactive oxygen (ROS) generation, lipid peroxidation, fluidity, intracellular calcium regulation, passive electrophysiological properties, long-term potentiation (LTP). disturbed integrity inducing ROS generation resulting decreased dysregulation, depolarization, impaired LTP. The damaging effects were significantly greater than those LMW-Aβ1-42. Therapeutic reduction may prevent progression ameliorating direct damage.-Yasumoto, T., Takamura, Y., Tsuji, M., Watanabe-Nakayama, Imamura, K., Inoue, H., Nakamura, S., Kimura, A., Yano, Nishijo, Kiuchi, Teplow, D. B., Ono, K. High molecular weight β1-42 induce neurotoxicity via plasma damage.