A beta(42) oligomers impair the bioenergetic activity in hippocampal synaptosomes derived from APP-KO mice

作者：Beckert Benedikt; Acker Palmer Amparo; Volknandt Walter

来源：Biological Chemistry, 2018, 399(5): 453-465.

DOI：10.1515/hsz-2017-0238

<jats:title>Abstract</jats:title>
<jats:p>Employing hippocampal synaptosomes from amyloid precursor protein (APP)-deleted mice we analyzed the immediate effects of amyloid beta peptide 42 (Aβ<jats:sub>42</jats:sub>) peptide in its oligomeric or fibrillar assembly or of soluble amyloid precursor protein alpha (sAPPα) protein on their bioenergetic activity. Upon administration of oligomeric Aβ<jats:sub>42</jats:sub> peptide for 30 min we observed a robust decrease both in mitochondrial activity and in mitochondrial membrane potential (MMP). In contrast the respective fibrillary or scrambled peptides showed no effect, indicating that inhibition strictly depends on the oligomerization status of the peptide. Hippocampal synaptosomes from old APP-KO mice revealed a further reduction of their already impaired bioenergetic activity upon incubation with 10 μ<jats:sc>m</jats:sc> Aβ<jats:sub>42</jats:sub> peptide. In addition we evaluated the influence of the sAPPα protein on mitochondrial activity of hippocampal synaptosomes derived from young or old APP-KO animals. In neither case 20 n<jats:sc>m</jats:sc> nor 200 n<jats:sc>m</jats:sc> sAPPα protein had an effect on mitochondrial metabolic activity. Our findings demonstrate that hippocampal synaptosomes derived from APP-KO mice are a most suitable model system to evaluate the impact of Aβ<jats:sub>42</jats:sub> peptide on its bioenergetic activity and to further elucidate the molecular mechanisms underlying the impairments by oligomeric Aβ<jats:sub>42</jats:sub> on mitochondrial function. Our data demonstrate that extracellular Aβ<jats:sub>42</jats:sub> peptide is taken up into synaptosomes where it immediately attenuates mitochondrial activity.</jats:p>

• 出版日期2018-5