Insulin-like growth factor 5 associates with human Ass plaques and promotes cognitive impairment

Risk factors such as dysregulation of Insulin-like growth factor (IGF) signaling have been linked to Alzheimer's disease. Here we show that Insulin-like Growth Factor Binding Protein 5 (Igfbp5), an inhibitory binding protein for insulin-like growth factor 1 (Igf-1) accumulates in hippocampal pyramidal neurons and in amyloid plaques in brains of Alzheimer patients. We investigated the pathogenic relevance of this finding with transgenic mice overexpressing Igfbp5 in pyramidal neurons of the brain. Neuronal overexpression of Igfbp5 prevents the training-induced increase of hippocampal and cortical Bdnf expression and reduces the effects of exercise on memory retention, but not on learning acquisition. Hence, elevated IGFBP5 expression could be responsible for some of the early cognitive deficits that occur during the course of Alzheimer's disease.

Automated summary

Risk factors such as dysregulation of Insulin-like growth factor (IGF) signaling have been linked to Alzheimer's disease. Here, it was found that Insulin-like Growth Factor Binding Protein 5 (Igfbp5) accumulates in hippocampal pyramidal neurons and in amyloid plaques in the brains of Alzheimer patients. Transgenic mice overexpressing Igfbp5 in pyramidal neurons were used to study its pathogenic relevance, and it was found that neuronal overexpression of Igfbp5 impairs the increase of hippocampal and cortical Bdnf expression induced by exercise and reduces exercise effects on memory retention, but not on learning acquisition. Therefore, elevated IGFBP5 expression may contribute to the early cognitive deficits in Alzheimer's disease.