%0 Generic %A Matioli, Maria Niures P.S. %A Nitrini, Ricardo %D 2018 %T Mechanisms linking brain insulin resistance to Alzheimer's disease %U https://scielo.figshare.com/articles/dataset/Mechanisms_linking_brain_insulin_resistance_to_Alzheimer_s_disease/7511978 %R 10.6084/m9.figshare.7511978.v1 %2 https://scielo.figshare.com/ndownloader/files/13941683 %K Alzheimer's disease %K diabetes mellitus %K insulin resistance %K neurodegeneration %K mechanisms %X

Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE) have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AβPP-Aβ oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection.

%I SciELO journals