Exogenous Aβ1-42 monomers improve synaptic and cognitive function in Alzheimer's disease model mice

作者：Duan, Yanhong; Lv, Junyan; Zhang, Zhonghui; Chen, Zhenzhen; Wu, Hao; Chen, Jinnan; Chen, Zhidong; Yang, Jiarun; Wang, Dasheng; Liu, Yamei; Chen, Fuxue; Tian, Yang; Cao, Xiaohua^*

来源：Neuropharmacology, 2022, 209: 109002.

DOI：10.1016/j.neuropharm.2022.109002

• Presenilins
• A beta(1-42)
• a7-nAchR
• Memory
• AD

Growing evidence has suggested the poor correlation between brain amyloid plaque and Alzheimer's disease (AD). Presenilin1 (PS1) and presenilin2 (PS2) conditional double knockout (cDKO) mice exhibited the reduced 42-amino acid amyloid-beta peptide (A beta(1-42)) level and AD-like symptoms, indicating a different pathological mechanism from the amyloid cascade hypothesis for AD. Here we found that exogenous synthetic A beta(1-42) monomers could improve the impaired memory not only in cDKO mice without A beta(1-42) deposition but also in the APP/PS1/Tau triple transgenic 3 x Tg-AD mice with A beta(1-42) deposition, which were mediated by alpha 7-nAChR. Our findings demonstrate for the first time that reduced soluble A beta(1-42) level is the main cause of cognitive dysfunction in cDKO mice, and support the opinions that low soluble A beta(1-42) level due to A beta(1-42) deposition may also cause cognitive deficits in 3 x Tg-AD mice. Therefore, "loss-of-function" of A beta(1-42) should be avoided when designing therapies aimed at reducing A beta(1-42) burden in AD.

• 单位
  上海大学