%0 Journal Article
%T Exogenous Aβ1-42 monomers improve synaptic and cognitive function in Alzheimer's disease model mice.
%A Duan Y
%A Lv J
%A Zhang Z
%A Chen Z
%A Wu H
%A Chen J
%A Chen Z
%A Yang J
%A Wang D
%A Liu Y
%A Chen F
%A Tian Y
%A Cao X
%A Duan Y
%A Lv J
%A Zhang Z
%A Chen Z
%A Wu H
%A Chen J
%A Chen Z
%A Yang J
%A Wang D
%A Liu Y
%A Chen F
%A Tian Y
%A Cao X
%J Neuropharmacology
%V 209
%N 0
%D 05 2022 15
%M 35196539
%F 5.273
%R 10.1016/j.neuropharm.2022.109002
%X 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.