P2‐027: Plasma protein associations with hippocampal atrophy across the cognitive spectrum from normal aging to Alzheimer's disease
Year: 2011
Type: article
Abstract: Prior work suggests a role of Apolipoprotein E (ApoE) in inflammation. We recently found that the levels of several plasma proteins involved in intracellular communication differ between ApoE4 carriers and non-carriers in a young cohort at-risk for familial AD (FAD). Here we investigate whether the plasma levels of these proteins correlate with hippocampal atrophy in the ADNI sample. We analyzed the imaging and plasma protein biomarker data from the Alzheimer's disease Neuroimaging Initiative (ADNI) study. Our sample included 475 subjects (244 ApoE4 carriers and 231 ApoE4 noncarriers). Baseline EDTA plasma samples were collected and analyzed with a 190 analyte multiplex immunoassay panel based on the Luminex xMAP platform. Hippocampal segmentations were generated from 1.5T 3D T1-weighted brain MRI scans with a novel automated segmentation technique based on the AdaBoost machine learning method. Hippocampal thickness was analyzed with the radial distance technique. We applied linear regression models to relate hippocampal radial distance to the plasma concentrations of several proteins found to have different levels in the CSF in ApoE4 carriers and non-carriers. We adjusted for effects of age and gender in the pooled sample, and separately in ApoE4 carriers and non-carriers. For multiple comparisons correction, we used permutations with threshold p < 0.01. High levels of interleukin 13 (IL13), a well-established inflammatory protein, showed a significant negative association with right hippocampal radial distance in the pooled sample (left ß = −0.21, p corrected = 0.44; right ß = −0.31, p corrected = 0.039). High levels of tissue inhibitor of metalloproteinases 1 (TIMP1), a protein that promotes cell proliferation and has an anti-apoptotic function, showed a significant negative association with hippocampal radial distance in the pooled sample on the left (ß = −0.42, p corrected = 0.027). Angiopoietin 2 (ANG2), a regulator of neuronal progenitor differentiation and migration, showed a significant positive association with hippocampal radial distance on the right in ApoE4 carriers (ß = 0.53, p corrected = 0.018), but a significant negative association on the left in ApoE4 non-carriers (ß = −0.2, p corrected = 0.026). Hippocampal atrophy in the ADNI cohort was associated with plasma levels of several proteins whose plasma levels were previously reported to differ between ApoE4 carriers and non-carriers in a FAD cohort. These plasma protein levels may inform pre-dementia diagnostic ascertainment in the future. Significance and β coefficient maps showing the association of IL13, TIMP1 and ANG2 serum concentrations with hippocampal radial distance in the pooled sample (N=475), ApoE4 carriers (N=244) and ApoE4 noncarriers (N=231).
Source: Alzheimer s & Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2020722975