AUTHOR=Bonham Luke W. , Geier Ethan G. , Steele Natasha Z. R. , Holland Dominic , Miller Bruce L. , Dale Anders M. , Desikan Rahul S. , Yokoyama Jennifer S. ,  Alzheimer’s Disease Neuroimaging Initiative 

TITLE=Insulin-Like Growth Factor Binding Protein 2 Is Associated With Biomarkers of Alzheimer’s Disease Pathology and Shows Differential Expression in Transgenic Mice

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 12 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.00476

DOI=10.3389/fnins.2018.00476

ISSN=1662-453X

ABSTRACT=There is increasing evidence that metabolic dysfunction plays an important role in Alzheimer’s disease (AD). Brain insulin resistance and subsequent impairment of insulin and insulin-like growth factor (IGF) signaling are thought to be linked with the neurodegenerative and clinical features of AD. Nevertheless, how the brain insulin/IGF signaling system is altered in AD and the effects of these changes on AD pathobiology are not well understood. IGF binding protein 2 (IGFBP-2) is an abundant cerebral IGF signaling protein and there is early evidence suggesting it associates with AD biomarkers. We evaluated the relationship between protein levels of IGFBP-2 with cerebrospinal fluid (CSF) biomarkers and neuroimaging markers of AD progression in 300 individuals from across the AD spectrum. CSF IGFBP-2 levels were correlated with CSF tau levels and brain atrophy in non-hippocampal regions. To further explore the role of IGFBP2 in tau pathobiology, we evaluated the expression of IGFBP2 brain tissue from transgenic mouse models of tauopathy (P301L-tau) as well as AD (TASTPM) and determined the cell types that most highly express IGFBP2. IGFBP2 expression in transgenic mouse models of neurodegenerative disease was only significantly different from wild-type mice in cortex, but not in hippocampus. In both humans and mice, IGFBP2 is most highly expressed in astrocytes. Taken together, our findings suggest that IGFBP-2 may be linked to tau pathology and provides further evidence for a relationship between metabolic dysregulation and neurodegeneration. Our results also raise the possibility that this relationship may extend beyond neurons.