Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease: a reference data set.
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.
Liang
Winnie S
WS
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.
Dunckley
Travis
T
Beach
Thomas G
TG
Grover
Andrew
A
Mastroeni
Diego
D
Ramsey
Keri
K
Caselli
Richard J
RJ
Kukull
Walter A
WA
McKeel
Daniel
D
Morris
John C
JC
Hulette
Christine M
CM
Schmechel
Donald
D
Reiman
Eric M
EM
Rogers
Joseph
J
Stephan
Dietrich A
DA
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
D016564:Amyloid beta-Protein Precursor; D018832:Molecular Chaperones; D011494:Protein Kinases