Premium
P2‐027: Plasma protein associations with hippocampal atrophy across the cognitive spectrum from normal aging to Alzheimer's disease
Author(s) -
Chow Nicole,
Hwang Kristy,
Ringman John,
Teng Edmond,
Thompson Paul,
Cole Greg,
Gylys Karen,
Jack Clifford,
Shaw Leslie,
Trojanowski John,
Soares Holly,
Weiner Michael,
Apostolova Liana
Publication year - 2011
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.2011.05.917
Subject(s) - hippocampal formation , alzheimer's disease neuroimaging initiative , apolipoprotein e , atrophy , neuroimaging , medicine , biomarker , neuroscience , alzheimer's disease , oncology , psychology , disease , biology , genetics
Methods: We analyzed the imaging and plasma protein biomarker data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. Our sample included 475 subjects – 58 normal controls, 310 MCI and 107 AD subjects of whom 244 were APOE4 carriers and 231 APOE4 non-carriers. 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 study the associations between IL13, TIMP1, and ANG2 plasma protein levels and hippocampal radial distance. Our linear regression models were adjusted for age and gender. We ran analyses in the pooled sample and then separately in APOE4 carriers and noncarriers. For multiple comparisons correction, we used permutations with threshold p<0.01. Results: High levels of IL13, a well-established inflammatory protein, showed a significant negative association with right hippocampal radial distance in the pooled sample (β=-0.31, pcorrected=0.039; Figure 1). High levels of 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 (β=-0.42, pcorrected=0.027, Figure 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 (β=0.53, pcorrected=0.018), but a significant negative association on the left in APOE4 non-carriers (β=-0.2, pcorrected=0.026, Figure 3).