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[P2–158]: IS THE PRESUBICULUM PROTECTED FROM NEURODEGENERATIVE CHANGES? A PATHOLOGICAL AND BIOCHEMICAL INVESTIGATION
Author(s) -
Murray Christina E.,
GamiPatel Priya,
Gkanatsiou Eleni,
Brinkmalm Gunnar,
Portelius Erik,
Blennow Kaj,
Ghiso Jorge,
Holton Janice,
Zetterberg Henrik,
Revesz Tamas,
Lashley Tammaryn
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.2017.06.809
Subject(s) - subiculum , entorhinal cortex , neurodegeneration , pathology , microglia , hippocampus , amyloid (mycology) , neuroscience , chemistry , biology , medicine , dentate gyrus , disease , immunology , inflammation
involves analysis of gene expression in late-onset Alzheimer’s disease (the most prevalent form of AD) relative to non-demented control cases. Previous studies have leveraged this strategy to identify a broad range of biological processes altered in disease. The patterns reflect a summation of differences in expression stemming from neurodegeneration, induction/repression, brain wide inflammation, and mismatched cohorts. We seek to identify changes most closely associated with neurodegeneration. Methods: We developed an approach to disaggregate expression data on the basis of regional severity, and to better control for variables of sex, age, post-mortem interval, and RNA integrity. Here we test the novel method using publically-available data sets collected from LOAD and control human specimens. Data preprocessing included singular value decomposition and principal component analysis to filter and normalize the data. Results:Up to 1000 transcripts were reprioritized on the basis of association with neurodegeneration. Prioritized transcripts included components of glutamatergic transmission, neurogenesis, and enzymes associated with maturation of the extracellular matrix. Neurodegeneration-associated transcripts also included markers of specific interneuron populations, and clarified the relationship between certain emerging biomarkers and AD neurodegeneration. Conclusions:The results indicate that novel insight into the LOAD neurodegeneration phenotype can be generated by prioritizing expression differences on the basis of regional severity.