Amyloid beta1-42(Aβ1-42) peptide, a major pathological component of Alzheimer's disease(AD), is known to locate and accumulate in the mitochondria.Research has demonstrated that nuclear transcription factors(nTF) play a direct or indirect role in the transcriptional regulation of mitochondria, which lose function in the early stages of neurodegenerative diseases.Based on this information, our study investigates the interactions between Aβ and nTFs in mitochondria.In this study, the interaction of 48 nTFs with Aβ was examined using a nTF-interaction kit. Mitochondrial lysate isolations were performed from 24 hours 0.1µM Aβ1-42 treated or untreated LUHMES cells differentiated into neurons.Immunoprecipitation(IP) with Aβ antibody was conducted on the mitochondrial lysates.IP samples were applied to the 96 wells of the kit containing specific probes for different nTFs' DNA binding sites.The interaction coefficients between Aβ and nTFs were determined based on the obtained signals.The most Aβ-interacting nTFs in treated and untreated groups were determined.In the Aβ1-42-treated group, 12 of 48 nTFs, namely AP2, ATF2, AP1, AR, BRN-3, CAR, HIF, PXR, P53, C/EBP, HNF4, and SMAD, were defined as the highly interacting nTFs with Aβ1-42 given that they exceed the upper limit of the 95% CI in the IP-based TF-interaction assay(Signosis).Aβ1-42 treatment may alter the Aβ-nTFs interaction pattern, causing changes in mitochondrial gene expression.Therefore, our results suggest a potential impact on early mitochondrial dysfunction in AD.The observation of a different nTF-Aβ interaction pattern in the control group compared to the Aβ-treated group implies a possible physiological function of Aβ in mitochondria.This study was supported by TUBITAK(ProjectID: 219Z179).