Mild inhibition of mitochondrial complex I reduces Tau pathology and improves energy homeostasis and synaptic function in human‐derived neurons of LOAD patients

LOAD neurons carrying ApoE4/4 alleles recapitulate LOAD phenotype allowing validation of a novel mitochondria-targeted therapeutics. These data support previous observations in AD mice demonstrating that mild inhibition of MCI induce mild energetic stress with subsequent activation of multifaceted adaptive stress response and neuroprotective mechanisms improving cellular energetics and mitochondrial morphofunction in LOAD human neurons. Further efforts will be focused on the determination of mechanisms of neuroprotection.