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

Lane EM, Hohman TJ, Jefferson AL, Alzheimer’s Disease Neuroimaging Initiative
Brain Imaging Behav. 2017 11 (6): 1779-1786

PMID: 27817134 · PMCID: PMC5419882 · DOI:10.1007/s11682-016-9636-0

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.

MeSH Terms (19)

Aged Aged, 80 and over Alzheimer Disease Amyloid beta-Peptides Apolipoprotein E4 Biomarkers Cognition Female Functional Laterality Hippocampus Humans Insulin-Like Growth Factor Binding Protein 2 Magnetic Resonance Imaging Male Middle Aged Neuropsychological Tests Organ Size Peptide Fragments tau Proteins

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