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Disturbances in insulin and possibly insulin growth factor-1 (IGF-1) signaling in the brain, especially the hippocampus, have been observed in Alzheimer¡¯s disease.

The deletion of insulin receptor and insulin receptor substrate (IRS)-2 in neurons delays brain growth and prevents memory dysfunction in mice by the ablation of the phosphoinositide-3-kinase/Akt/ mammalian
target of rapamycin (mTOR) pathway in neurons .

The activation of mTOR suppresses the autophagic process in neurons and high concentrations of potentially toxic ¦Â-amyloid and tau proteins are sustained in the neurons .

However, by contrast, both IRS-1 and IRS-2 expressions decrease in neurons of humans with Alzheimer¡¯s disease and both insulin and IGF-1 signaling are patently disturbed in brains affected by Alzheimer¡¯s disease.

Type 2 diabetic patients have increased levels of hyperphosphorylated tau in their brains that facilitate the formation of neurofibrillary tangles that induce cognitive dysfunction .

Induction of experimental diabetes with streptozotocin or analogous drugs increases the levels of ¦Â-amyloid and tau phosphorylation in rodents.

Thus, the proper maintenance of insulin receptor signaling in the hippocampus plays an important role in cognitive function.
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