Serum Insulin-Like Growth Factor I Deficiency Associates to Alzheimer's Disease Co-Morbidities

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Zegarra-Valdivia, JA
Santi, A
de Sevilla, MEF
Nunez, A
Aleman, IT
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IOS Press, Inc.
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Increasing evidence supports the notion that Alzheimer's disease (AD), a condition that presents heterogeneous pathological disturbances, is also associated to perturbed metabolic function affecting insulin and insulin-like growth factor I (IGF-I). While impaired insulin activity leading to insulin resistance has been associated to AD, whether altered IGF-I function affects the disease is not entirely clear. Despite the limitations of mouse models to mimic AD pathology, we took advantage that serum IGF-I deficient mice (LID mice) present many functional perturbations present in AD, most prominently cognitive loss, which is reversed by treatment with systemic IGF-I. We analyzed whether these mice display other pathological traits that are usual co-morbidities of AD. We found that LID mice not only display cognitive disturbances, but also show altered mood and sociability, increased susceptibility to epileptiform activity, and a disturbed sleep/wake cycle. Collectively, these data suggest that reduced IGF-I activity contributes to heterogeneous deficits commonly associated to AD. We suggest that impaired IGF-I activity needs to be taken into consideration when modeling this condition.
We are thankful to M. Garcia for technical support. This work was funded by a grant from Ciberned, by and Inter-CIBER project (PIE14/00061), and from SAF2016-76462-C2-1-P (MINECO). J.A. ZegarraValdivia acknowledges the financial support from the National Council of Science, Technology and Technological Innovation (CONCYTEC, Peru) through ´the National Fund for Scientific and Technological Development (FONDECYT, Peru). ´Authors’ disclosures available online (
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insulin-like growth factor 1, Alzheimer’s disease, animal models of disease, co-morbidities