IGF1 deficiency integrates stunted growth and neurodegeneration in Down syndrome
New research from the Linda Crnic Institute for Down syndrome identified an important deletion of “insulin-like growth factor 1” (IGF1), a master regulator of growth and brain development, as the top biosignature associated with neurodegeneration in Down syndrome. The study titled IGF1 deficiency integrates stunted growth and neurodegeneration in Down syndrome was recently published in Cell Reports. The study was funded by a generous National Institutes of Health INCLUDE grant.
A multidisciplinary team of scientists at the Crnic Institute set out to identify mechanisms underlying neurodegeneration in individuals with Down syndrome through the Crnic Institute Human Trisome ProjectTM, a large cohort study of individuals with Down Syndrome and neurotypical controls. The team analyzed diverse biomarkers of neurological impairment and brain inflammation in 419 study participants, of which over 300 have Down syndrome. They correlated the biomarkers to thousands of data points obtained through multi-omics assays of the same blood samples. These unbiased analyses revealed that individuals with Down syndrome with the highest markers of neurological impairment and brain inflammation displayed markedly low levels of IGF1.
Furthermore, the study revealed that, despite producing normal levels of the growth hormone, individuals with Down syndrome display chronic IGF1 deficiency across the lifespan, with shorter children with Down syndrome presenting both stronger IGF1 deficiency and higher markers of neurological impairment.