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P1–199: MicroRNA biomarkers in Alzheimer's disease
Author(s) -
Mistrellides Costas,
Lun Katie,
Sattlecker Martina,
Schalkwyk Leonard,
Soininen Hilkka,
Kloszewska Iwona,
Mecocci Patrizia,
Tsolaki Magda,
Vellas Bruno,
Lovestone Simon,
Hodges Angela
Publication year - 2013
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.2013.05.422
Subject(s) - disease , microrna , medicine , biology , genetics , gene
the association between regional cortical thinning (CT) measured by Magnetic Resonance Imaging (MRI) and brain amyloidosis (measured by CSF Ab 1-42 concentrations), or tau hyperphosphorylation (tau 181; p-tau) in Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) patients. We test the hypothesis that the association between cortical thinning, amyloidosis or tau hyperphosphorylation depends on cortical regions and clinical stages of AD.Methods: T1-weighed MRIs and associated CSF markers from individuals with mild cognitive impairment (MCI; 16), Alzheimer Disease (AD; n1⁄47) and age-matched cognitively normal subjects (CN; n1⁄48) were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Cortical surface reconstruction and group registration were generated using Freesurfer. A general linear model was used to conduct regressions between CSFmarkers and cortical thickness.Results: Correlation analyses in the MCI group showed a positive correlation between CT and Ab 1-42 measures predominantly in the temporo-parietal regions, namely the precuneus (peak r1⁄40.67; p<0.01) and the fusiform (peak r1⁄40.85; p<0.0001). Similar but smaller effects were present in AD, with additional clusters in the frontal cortex (peak r1⁄40.94; p1⁄40.0001). In both MCI and AD groups, significant clusters of negative correlations between CTand p-tau were mainly found in medio-temporal and dorso-lateral prefrontal areas. In the CN group, no relationship was observed between cortical thickness and either CSF biomarkers. Conclusions: Although limited by sample sizes, our results suggest a posterior-anterior gradient of structural vulnerability to A b 1-42. Alternatively, weaker temporo-parietal effect between CT and Ab 1-42 in AD relative toMCI, likely results from a ceiling effect of Ab 1-42 levels in the AD group. Conversely, a frontal effect can only be found in the AD group, which possibly corresponds to a later stage of Ab 1-42 -driven neurodegeneration.