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[P2–199]: MAPPING PROTEIN‐PROTEIN INTERACTIONS BY PEPTIDE ARRAY FOR DISRUPTOR PEPTIDE DEVELOPMENT AND TRANSLATIONAL IMPACT!
Author(s) -
Elliott Christina,
Baillie George S.,
Killick Richard
Publication year - 2017
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.2017.06.850
Subject(s) - peptide , protein–protein interaction , alanine scanning , biology , biochemistry , chemistry , microbiology and biotechnology , computational biology , gene , mutagenesis , mutation
Background: The role of vascular disease in Alzheimer’s disease (AD) is still debated. White matter hypointensity (WMH) volume is an imaging measure of vascular burden. Using MRI and Positron Emission Tomography (PET) we examined the voxel-level relationships betweenWMHand 3 key processes inAD: amyloid deposition, tau aggregation and microglial activation. Methods: 15 participants with a clinical diagnosis of AD had T1-weighted MRI, F-flutemetamol, F-AV1451 and C-PBR28 PET scans. 18 healthy controls also had F-flutemetamol and C-PBR28 scans, and 8 of these also had F-AV1451 PET. Z-score maps for each tracer (80-100 minute ratio image for F-AV1451, 90-120 minute ratio image for F-flutemetamol and logan Vd parametric map for C-PBR28 ) were calculated for the AD subjects compared to the controls for each tracer.WMHvolumes from theMRIwere calculated from Freesurfer software. Multiple regression in SPM8 was used to calculate voxel wise correlations between WMH volume and tracer uptake. A pvalue of p<0.05 was considered significant. Results:Amyloid deposition: there were correlations between WMH volume and amyloid deposition in the 1) frontal lobe (right medial and anterior orbital gyri, left posterior orbital gyrus, and right superior frontal gyri) 2) parietal lobe (left superior parietal gyrus) and 3) corpus callosum. Tau aggregation: there were correlations between WMH burden and tau aggregation in the left and right posterior temporal lobe Microglial activation :there were correlations between WMH volume and microglial activation in the 1) frontal lobe (right superior/middle frontal gyrus, right subgenual frontal cortex, right medial orbital gyrus) 2) parietal lobe (postcentral / precentral gyrus, left inferolateral part of parietal lobe and 3) occipital lobe (left lateral part of occipital lobe). Conclusions:White matter hypointensity volume correlates at voxel-level with amyloid deposition, tau aggregation and microglial activation. These findings emphasise the complex disease pathogenesis occurring in AD, and the need for a multi-targeted treatment.