Am J Geriatr Psychiatry 13:12, December 2005 1041 REGULAR RESEARCH ARTICLES Transcriptome Differences Between the Frontal Cortex and Hippocampus of Wild- Type and Humanized Presenilin-1 Transgenic Mice Travis Unger, B.S., Zeljka Korade, Ph.D., D.V.M. Orly Lazarov, Ph.D., David Terrano, B.S. Nina F. Schor, M.D., Ph.D., Sangram S. Sisodia, Ph.D. Ka ´ roly Mirnics, M.D. Objective: The authors investigated the differences between the frontal cortical (Fc) and hippocampal (Hc) transcriptomes of wild type (wt mPS1), humanized presenilin- 1 (PS1 [wt hPS1]) and Alzheimer-disease (AD)–linked DE9 hPS1 mutant mice. Meth- ods: Using high-density oligonucleotide arrays, they recently performed transcriptome profiling of wt mPS1, wt hPS1, and DE9 hPS1 mutant mice. Whereas these studies analyzed the commonalities of gene expression patterns and commonly-regulated genes across the two brain areas and across the animal models, the current study focused on the gene-expression differences across Fc and Hc, two critical AD-affected brain regions. Results: The data revealed that in the wild-type mice, there are signifi- cant transcriptome differences between the Fc and the Hc tissue, and these expression differences are maintained in humanized transgenic mice carrying the wt hPS1 gene or DE9 hPS1 mutation. Also, they provide evidence that a subset of genes show dis- turbed regional Fc–Hc gene-expression ratios in the transgenic mice carrying the DE9 hPS1 mutation. Some of these genes, including stearoyl-Coenzyme A desaturase-2 (Scd2) and Prostaglandin D2 synthase (Ptgds), have been previously implicated in the pathology of AD. Conclusions: Data suggest that disturbed gene-expression ratios between cortical regions may be an important event in altered brain physiology. (Am J Geriatr Psychiatry 2005; 13:1041–1051) Received January 27, 2005; revised, accepted March 8, 2005. From the Depts. of Psychiatry (TU, KM), Neurobiology (KM), and Pediatrics (ZK, NFS), Univ. of Pittsburgh School of Medicine, Pittsburgh, PA; and the Center for Molecular Neurobiology, Univ. of Chicago, Chicago,IL (OL,DT, SSS). Send correspondence and reprint requests to Ka ´roly Mirnics, M.D., Dept. of Psychiatry, Univ. of Pittsburgh School of Medicine, E1453 Biomedical Science Tower, Pittsburgh,PA 15261. e-mail: karoly@pitt.edu  2005 American Association for Geriatric Psychiatry O ver the last several years, DNA microarrays have revolutionized RNA-profiling studies. 1–4 Although these studies are greatly complicated by the underlying tissue complexity, expression-profiling of brain tissue has provided numerous leads toward better understanding of CNS-expression diversity, 5–9