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IC‐P‐158: MARKERS OF INFLAMMATION AND VASCULAR DYSFUNCTION ARE DIFFERENTIALLY ASSOCIATED WITH HIPPOCAMPAL VOLUME BY COGNITIVE STATUS IN ADNI
Author(s) -
Neth Bryan J.,
Casanova Ramon,
Hughes Timothy,
Craft Suzanne
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.165
Subject(s) - inflammation , medicine , pathogenesis , hippocampal formation , neuroimaging , endocrinology , oncology , pathology , psychiatry
Background: Inflammation and vascular dysfunction have been shown to play a role in the pathogenesis of various neurodegenerative diseases, including Alzheimer’s disease (AD). This study examined the association between total hippocampal volume (HV) and plasma levels of proteins involved in inflammation and vascular injury that may contribute to mild cognitive impairment (MCI) and AD.Methods: Alzheimer’s Disease Neuroimaging Initiative-1 (ADNI-1) structural MRI and plasma proteomic data sets were used in this study. Data from 488 ADNI-1 participants were studied, from three diagnostic groups based upon cognitive status: 49 cognitively normal (CN) adults, 330 adults with MCI, and 109 adults with AD. Baselinemeasurements of HVwere determined using FreeSurfer and downloaded from the ADNI website. Multiple linear regression was performed to search for associations of 36 plasma proteins involved in inflammation and vascular dysfunction with HV for each of the diagnostic groups, adjusted for age, gender, and BMI. Results: For 10 of the 36 proteins analyzed, higher plasma levels were associated with smaller baseline HV in at least one of the three diagnostic groups. Higher levels of two proteins were significantly associated with smaller HV in more than one group: CD40 antigen (CD40) in MCI (p<0.01) and AD (p<0.05); and Intercellular Adhesion Molecule-1 (ICAM-1) in CN (p<0.05) and MCI (p<0.05). Levels of beta-2-microglobulin (B2M, p<0.005), Vascular Cellular Adhesion Molecule-1 (VCAM1, p<0.005), Macrophage Inflammatory Protein-1-alpha (MIP-1-alpha, p<0.001), Interleukin-18 (IL-18, p<0.05), and Matrix Metalloproteinase1/2 (MMP-1/2, p<0.05/p<0.01) were associated with HV in CN, whereas Growth-Regulated alpha protein (GRO-alpha, p<0.05) and Plasminogen Activator Inhibitor-1 (PAI-1, p<0.05) were associated with HV in MCI. Conclusions: Higher plasma levels of 10-of-36 proteins were associated with smaller baseline HV in at least one diagnostic group. These results support previous findings of increased neuroinflammation in MCI and AD, and highlight the potential role of vascular injury. Furthermore, our results may support the importance of inflammatory processes in the early-stage pathogenesis of AD, as 9-of-10 of the associations occurred only in the CN/MCI groups. Validation of these findings with an independent data set is needed to further characterize the association of vascular biomarkers and brain changes associated with MCI/AD.