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Serum insulin-like growth factor I regulates brain amyloid-β levels

Nature Medicine volume 8, pages 13901397 (2002) | Download Citation

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Abstract

Levels of insulin-like growth factor I (IGF-I), a neuroprotective hormone, decrease in serum during aging, whereas amyloid-β (Aβ), which is involved in the pathogenesis of Alzheimer disease, accumulates in the brain. High brain Aβ levels are found at an early age in mutant mice with low circulating IGF-I, and Aβ burden can be reduced in aging rats by increasing serum IGF-I. This opposing relationship between serum IGF-I and brain Aβ levels reflects the ability of IGF-I to induce clearance of brain Aβ, probably by enhancing transport of Aβ carrier proteins such as albumin and transthyretin into the brain. This effect is antagonized by tumor necrosis factor-α, a pro-inflammatory cytokine putatively involved in dementia and aging. Because IGF-I treatment of mice overexpressing mutant amyloid markedly reduces their brain Aβ burden, we consider that circulating IGF-I is a physiological regulator of brain amyloid levels with therapeutic potential.

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Acknowledgements

We thank R.J. Sancho and F. Lozano for expert help; and A. Nuñez for help in measuring culture resistances. This work was supported by grants from FISS (01/1188) and CAM (08.5/0039/2000).

Author information

Affiliations

  1. Laboratory of Neuroendocrinology, Cajal Institute, CSIC, Madrid, Spain

    • E. Carro
    • , J.L. Trejo
    •  & I. Torres-Aleman
  2. Clinica Universitaria de Navarra, Universidad de Navarra, Pamplona, Spain

    • T. Gomez-Isla
  3. Clinical Endocrinology Branch, National Institutes of Health, Bethesda, Maryland, USA

    • D. LeRoith

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Competing interests

E.C. and I.T.-A. in conjunction with the CSIC and Complutense University of Madrid have applied for a patent, in Spain, which includes a process to use IGF-I in several neurodegenerative conditions. In addition, I.T.-A. is a founder of Policlonal SL which has licensed this patent.

Corresponding author

Correspondence to I. Torres-Aleman.

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DOI

https://doi.org/10.1038/nm1202-793

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