title: Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease: a reference data set.
abstract: Alzheimer's Disease (AD) is the most widespread form of dementia during the later stages of life. If improved therapeutics are not developed, the prevalence of AD will drastically increase in the coming years as the world's population ages. By identifying differences in neuronal gene expression profiles between healthy elderly persons and individuals diagnosed with AD, we may be able to better understand the molecular mechanisms that drive AD pathogenesis, including the formation of amyloid plaques and neurofibrillary tangles. In this study, we expression profiled histopathologically normal cortical neurons collected with laser capture microdissection (LCM) from six anatomically and functionally discrete postmortem brain regions in 34 AD-afflicted individuals, using Affymetrix Human Genome U133 Plus 2.0 microarrays. These regions include the entorhinal cortex, hippocampus, middle temporal gyrus, posterior cingulate cortex, superior frontal gyrus, and primary visual cortex. This study is predicated on previous parallel research on the postmortem brains of the same six regions in 14 healthy elderly individuals, for which LCM neurons were similarly processed for expression analysis. We identified significant regional differential expression in AD brains compared with control brains including expression changes of genes previously implicated in AD pathogenesis, particularly with regard to tangle and plaque formation. Pinpointing the expression of factors that may play a role in AD pathogenesis provides a foundation for future identification of new targets for improved AD therapeutics. We provide this carefully phenotyped, laser capture microdissected intraindividual brain region expression data set to the community as a public resource.
authors.affiliation: Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.
authors.forename: Winnie S
authors.initials: WS
authors.lastname: Liang
authors.forename: Travis
authors.initials: T
authors.lastname: Dunckley
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.forename: Andrew
authors.initials: A
authors.lastname: Grover
authors.forename: Diego
authors.initials: D
authors.lastname: Mastroeni
authors.forename: Keri
authors.initials: K
authors.lastname: Ramsey
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Caselli
authors.forename: Walter A
authors.initials: WA
authors.lastname: Kukull
authors.forename: Daniel
authors.initials: D
authors.lastname: McKeel
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Christine M
authors.initials: CM
authors.lastname: Hulette
authors.forename: Donald
authors.initials: D
authors.lastname: Schmechel
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.forename: Joseph
authors.initials: J
authors.lastname: Rogers
authors.forename: Dietrich A
authors.initials: DA
authors.lastname: Stephan
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology; D011494:Protein Kinases / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016564:Amyloid beta-Protein Precursor; D018832:Molecular Chaperones; D011494:Protein Kinases