Insulin-like growth factor binding protein-2 interactions with Alzheimer’s disease biomarkers

• DOI: 10.1007/s11682-016-9636-0
• Publication Date: 2016-11-05T12:15:50Z
• Authors: Elizabeth M. Lane; Timothy J. Hohman; Angela L. Jefferson
• Keywords: Aged, 80 and over; Male; Amyloid beta-Peptides; Apolipoprotein E4; tau Proteins; Organ Size; Middle Aged; Neuropsychological Tests; Hippocampus; Magnetic Resonance Imaging; Functional Laterality; Peptide Fragments; 3. Good health; Insulin-Like Growth Factor Binding Protein 2; 03 medical and health sciences; Cognition; 0302 clinical medicine; Alzheimer Disease; Humans; Female; Biomarkers; Aged

Plasma levels of insulin-like growth factor binding protein-2 (IGFBP-2) have been associated with Alzheimer's disease (AD) and brain atrophy. Some evidence suggests a potential synergistic effect of IGFBP-2 and AD neuropathology on neurodegeneration, while other evidence suggests the effect of IGFBP-2 on neurodegeneration is independent of AD neuropathology. Therefore, the current study investigated the interaction between plasma IGFBP-2 and cerebrospinal fluid (CSF) biomarkers of AD neuropathology on hippocampal volume and cognitive function. AD Neuroimaging Initiative data were accessed (n = 354, 75 ± 7 years, 38 % female), including plasma IGFBP-2, CSF total tau, CSF Aβ-42, MRI-quantified hippocampal volume, and neuropsychological performances. Mixed effects regression models evaluated the interaction between IGFBP-2 and AD biomarkers on hippocampal volume and neuropsychological performance, adjusting for age, sex, education, APOE ε4 status, and cognitive diagnosis. A baseline interaction between IGFBP-2 and CSF Aβ-42 was observed in relation to left (t(305) = -6.37, p = 0.002) and right hippocampal volume (t(305) = -7.74, p = 0.001). In both cases, higher IGFBP-2 levels were associated with smaller hippocampal volumes but only among amyloid negative individuals. The observed interaction suggests IGFBP-2 drives neurodegeneration through a separate pathway independent of AD neuropathology.