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Type 2 Diabetes Mellitus (DM) and Alzheimers disease (AD) share epidemiological and biochemical features.Specifically, both diseases are amyloidoses or conformational diseases as they are characterized by insoluble protein aggregates with a fibrillar conformation-amylin in Type 2 diabetes pancreatic islets, and Aβ amyloid and tau-containing neurofibrillary tangles in Alzheimers brains.Amylin aggregation is associated with pancreatic β-cell loss, Whereas Aβ and tangle formation is associated with neuronal cell loss.Patients with DM have a higher risk of developing AD later on in life, prompting suggestions that AD is a form of neuronal DM.Cell culture, proteomics and functional assays were employed to investigate what common neuronal protein targets are deregulated by Aβ and human amylin.Aβ and human amylin were found to deregulate key proteins associated with mitochondrial, respiration, cytoskeleton and cell cycle amongst others.Exposure to Aβ and human amylin was found to significantly impair the.function of overlapping mitochondrial complexes, in the absence of significant cell death.The results indicate that mitochondrial dysfunction is an early neurotoxicity event exerted by both Aβ and human amylin.Our results suggest that mitochondrial dysfunction may contribute to the increased risk of AD in DM patients.Together, the results suggest that restoring mitochondrial function may be beneficial for both AD and DM.