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IC‐P‐171: Dynamic optical imaging of a cleavable CPP‐bound, dual‐NIR fluorescent/MRI probe targeting cathepsin D
Author(s) -
Snir Jonatan,
Suchy Mojmir,
Li Alex X.,
St. Lawrence Keith,
Hudson Robert,
Pasternak Stephen,
Bartha Robert
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.2013.05.168
Subject(s) - in vivo , washout , fluorescence , cathepsin d , chemistry , cathepsin b , biophysics , genetically modified mouse , cathepsin , wild type , cleavage (geology) , microbiology and biotechnology , transgene , biochemistry , mutant , biology , enzyme , medicine , physics , quantum mechanics , gene , paleontology , fracture (geology)
memory complaints, MMSE 26 and CDR1⁄40), 100 MCI (MMSE 24 and CDR1⁄40.5, memory impairment based on Rey Auditory Verbal Learning Test and that did not meet DSM IV criteria for AD dementia) and 198 AD (12 MMSE 26 and CDR 0.5 and meeting DSM IV criteria). Subjects with other types of dementia and/or non-AD grounds for cognitive issues were not offered to participate. Clinical data, neuropsychological tests and biomarkers (blood, urine and CSF whenever possible) will be collected at Baseline and every 6 months until Month 48. MRI scans (3DT1, 3DT2, FLAIR, SWI, DWI and DTI) will be collected up to 3 times between Baseline and Month 48, using a Philips Achieva 3T scanner, for consenting subjects (n1⁄4158). The volume of intracranial cavity (ICV), left and right hippocampi (HCV), lateral ventricles (LVV) and whole brain (WBV) were assessed at Baseline using an automated multi-atlas segmentation algorithm. Descriptive statistics of HCV, LVV and WBV were computed for each group after normalization by ICV. Difference between groups was assessed using an ANCOVA, with age and ICV as covariates, and by ROC analysis. Results: HCV, LVVand WBV results are listed in Table 1. Significant differences (p<0.05) were found between each group, except for LVV between MCI and AD (see Fig.1a-c). ROC analysis showed best group separation for HCV between NC and AD (AUC1⁄40.89, see Fig.1d). HCV was also the best endpoint to separate NC and MCI (AUC1⁄40.71), while WBV best separatedMCI and AD (AUC1⁄40.72).Conclusions:BaselineMRI endpoints showed significant differences between NC, MCI and AD. Disease progression will be monitored, among others, through conversion to dementia and evolution of volumetric MRI biomarkers. The study will provide valuable clinical, biological and MRI data on a large sample of elderly subjects. The monocentric aspect of the study will help decrease variability.