Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease: A reference data set

Winnie S. Liang, Travis Dunckley, Thomas G. Beach, Andrew Grover, Diego Mastroeni, Keri Ramsey, Richard J. Caselli, Walter A. Kukull, Daniel McKeel, John C. Morris, Christine M. Hulette, Donald Schmechel, Eric M. Reiman, Joseph Rogers, Dietrich A. Stephan

Research output: Contribution to journalArticle

163 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)240-256
Number of pages17
JournalPhysiological Genomics
Volume33
Issue number2
DOIs
StatePublished - Apr 22 2008
Externally publishedYes

Fingerprint

Alzheimer Disease
Gene Expression
Brain
Laser Capture Microdissection
Datasets
Neurons
Entorhinal Cortex
Neurofibrillary Tangles
Gyrus Cinguli
Amyloid Plaques
Human Genome
Visual Cortex
Temporal Lobe
Prefrontal Cortex
Transcriptome
Dementia
Hippocampus
Lasers
Therapeutics
Research

Keywords

  • Affymetrix microarrays
  • Expression profiling
  • Laser capture microdissection
  • Neuron

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease : A reference data set. / Liang, Winnie S.; Dunckley, Travis; Beach, Thomas G.; Grover, Andrew; Mastroeni, Diego; Ramsey, Keri; Caselli, Richard J.; Kukull, Walter A.; McKeel, Daniel; Morris, John C.; Hulette, Christine M.; Schmechel, Donald; Reiman, Eric M.; Rogers, Joseph; Stephan, Dietrich A.

In: Physiological Genomics, Vol. 33, No. 2, 22.04.2008, p. 240-256.

Research output: Contribution to journalArticle

Liang, WS, Dunckley, T, Beach, TG, Grover, A, Mastroeni, D, Ramsey, K, Caselli, RJ, Kukull, WA, McKeel, D, Morris, JC, Hulette, CM, Schmechel, D, Reiman, EM, Rogers, J & Stephan, DA 2008, 'Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease: A reference data set', Physiological Genomics, vol. 33, no. 2, pp. 240-256. https://doi.org/10.1152/physiolgenomics.00242.2007
Liang, Winnie S. ; Dunckley, Travis ; Beach, Thomas G. ; Grover, Andrew ; Mastroeni, Diego ; Ramsey, Keri ; Caselli, Richard J. ; Kukull, Walter A. ; McKeel, Daniel ; Morris, John C. ; Hulette, Christine M. ; Schmechel, Donald ; Reiman, Eric M. ; Rogers, Joseph ; Stephan, Dietrich A. / Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease : A reference data set. In: Physiological Genomics. 2008 ; Vol. 33, No. 2. pp. 240-256.
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