{Reference Type}: Journal Article
{Title}: Exogenous Aβ1-42 monomers improve synaptic and cognitive function in Alzheimer's disease model mice.
{Author}: Duan Y;Lv J;Zhang Z;Chen Z;Wu H;Chen J;Chen Z;Yang J;Wang D;Liu Y;Chen F;Tian Y;Cao X;Duan Y;Lv J;Zhang Z;Chen Z;Wu H;Chen J;Chen Z;Yang J;Wang D;Liu Y;Chen F;Tian Y;Cao X;
{Journal}: Neuropharmacology
{Volume}: 209
{Issue}: 0
{Year}: 05 2022 15
{Factor}: 5.273
{DOI}: 10.1016/j.neuropharm.2022.109002
{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.