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Article Info.
2009.08.31; 42(8) pp. 475~481

Insulin resistance and Alzheimer¡¯s disease


Suzanne M. de la Monte*  


Departments of Neurology, Pathology, and Medicine, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Providence, RI, USA  


Emerging data demonstrate pivotal roles for brain insulin resistance and insulin deficiency as mediators of cognitive impairment and neurodegeneration, particularly Alzheimer¡¯s disease (AD). Insulin and insulin-like growth factors (IGFs) regulate neuronal survival, energy metabolism, and plasticity, which are required for learning and memory. Hence, endogenous brain-specific impairments in insulin and IGF signaling account for the majority of AD-associated abnormalities. However, a second major mechanism of cognitive impairment has been linked to obesity and Type 2 diabetes (T2DM). Human and experimental animal studies revealed that neurodegeneration associated with peripheral insulin resistance is likely effectuated via a liver-brain axis whereby toxic lipids, including ceramides, cross the blood brain barrier and cause brain insulin resistance, oxidative stress, neuro-inflammation, and cell death. In essence, there are dual mechanisms of brain insulin resistance leading to AD-type neurodegeneration: one mediated by endogenous, CNS factors; and the other, peripheral insulin resistance with excess cytotoxic ceramide production. [BMB reports 2009; 42(8): 475-481]  


Alzheimer¡¯s disease, Central nervous system, Ceramid, Diabetes mellitus, Insulin resistance, Neurodegeneration, Non-alcoholic steatohepatitis, Obesity, Streptozotocin