Insulin-like growth factor binding protein-2 interactions with Alzheimer's disease biomarkers.
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.
Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, 1207 17th Avenue South, Suite 204, Nashville, TN, 37212, USA.
Elizabeth M
EM
Lane
Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, 1207 17th Avenue South, Suite 204, Nashville, TN, 37212, USA.
Timothy J
TJ
Hohman
Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, 1207 17th Avenue South, Suite 204, Nashville, TN, 37212, USA. angela.jefferson@vanderbilt.edu.
Angela L
AL
Jefferson
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D003071:Cognition; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000000981:diagnostic imaging; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009929:Organ Size; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; C577903:IGFBP2 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
Alzheimer’s disease; Hippocampus; Insulin-like growth factor binding protein-2; Insulin-like growth factor-I; Insulin-like growth factor-II; Memory