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P3‐148: Systematic Review of Genome‐Wide Studies in Alzheimer’s Disease and Prioritization of Candidate Pathways Using an Integrative Systems Biology Approach
Author(s) -
Talwar Puneet,
Kukreti Ritushree
Publication year - 2016
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.2016.06.1808
Subject(s) - computational biology , genome wide association study , genome , disease , biology , gene , candidate gene , epigenome , biological pathway , prioritization , genomics , bioinformatics , genetics , medicine , genotype , dna methylation , gene expression , single nucleotide polymorphism , pathology , management science , economics
with positive beta-amyloid deposition on PiB PET, defined using a standardized uptake value ratio (SUVR) of 1.5, were included. All voxels in the PiB-PET images were divided by median uptake in cerebellum and transformed into template space. Partial volume correction (PVC) was performed. Voxel-level comparisons were performed across groups both with and without PVC using SPM5.Results were assessed after correction for multiple comparisons using family-wise error at p<0.05. Subjects also completed memory, language, and visuospatial tests that may have been used to augment DATand PCA diagnosis, but was not used in diagnosis of LPA. Results:Cognitively, DAT subjects had poorer memory than lvPPA and PCA subjects, lvPPA subjects had poorer language scores than DAT and PCA subjects, and PCA had poorer visuospatial scores that lvPPA and DAT subjects. The groups did not differ on global SUVR. Regional distribution of PiB-PET was similarly widespread in each of the three groups, although PCA showed greater uptake in bilateral occipital lobe compared to DAT, and greater uptake in right occipital lobe compared to lvPPA. These findings were observed both with and without PVC. No other regional PiB-PET differences were observed across groups. Conclusions:These findings suggest that while beta-amyloid deposition is typically diffuse in Alzheimer’s disease variants, regional differences exist as compared to DAT, although this DAT group may represent those with an earlier onset. The occipital lobe is particularly vulnerable to beta-amyloid deposition, as well as neurodegeneration, in PCA.