Exogenous Aβ1-42 monomers improve synaptic and cognitive function in Alzheimer's disease model mice. (15th May 2022)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Neuropharmacology. Volume 209(2022)
• Publication Date: 2022-05-15
• Subjects: Presenilins -- Aβ1-42 -- a7-nAchR -- Memory -- AD; AD Alzheimer's disease -- Aβ1-42 42-amino acid amyloid-β peptide -- 3×Tg APP/PS1/Tau triple transgenic -- α7-nAChR α7-nicotinic acetylcholine receptor -- AMPAR amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid subtype glutamate receptor -- NMDAR N-methyl-D-aspartic acid receptor; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2022.109002
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: 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-β peptide (Aβ1-42 ) level and AD-like symptoms, indicating a different pathological mechanism from the amyloid cascade hypothesis for AD. Here we found that exogenous synthetic Aβ1-42 monomers could improve the impaired memory not only in cDKO mice without Aβ1-42 deposition but also in the APP/PS1/Tau triple transgenic 3 × Tg-AD mice with Aβ1-42 deposition, which were mediated by α7-nAChR. Our findings demonstrate for the first time that reduced soluble Aβ1-42 level is the main cause of cognitive dysfunction in cDKO mice, and support the opinions that low soluble Aβ1-42 level due to Aβ1-42 deposition may also cause cognitive deficits in 3 × Tg-AD mice. Therefore, "loss-of-function" of Aβ1-42 should be avoided when designing therapies aimed at reducing Aβ1-42 burden in AD. Highlights: cDKO mice exhibit the reduced Aβ1-42 level and AD-like symptoms. Aβ1-42 monomers improve the impaired synaptic efficacy of cDKO mice. Aβ1-42 monomers improve the impaired cognitive function of cDKO mice. α7-nAChR mediated the effect of Aβ1-42 monomers on the memory of cDKO and 3 × Tg-AD mice.