Neuronal gene expression in non-demented individuals with intermediate Alzheimer's Disease neuropathology

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

52 Scopus citations

Abstract

While the clinical and neuropathological characterization of Alzheimer's Disease (AD) is well defined, our understanding of the progression of pathologic mechanisms in AD remains unclear. Post-mortem brains from individuals who did not fulfill clinical criteria for AD may still demonstrate measurable levels of AD pathologies to suggest that they may have presented with clinical symptoms had they lived longer or are able to stave off disease progression. Comparison between such individuals and those clinically diagnosed and pathologically confirmed to have AD will be key in delineating AD pathogenesis and neuroprotection. In this study, we expression profiled laser capture microdissected non-tangle bearing neurons in 6 post-mortem brain regions that are differentially affected in the AD brain from 10 non-demented individuals demonstrating intermediate AD neuropathologies (NDAD; Braak stage of II through IV and CERAD rating of moderate to frequent) and evaluated this data against that from individuals who have been diagnosed with late onset AD as well as healthy elderly controls. We identified common statistically significant expression changes in both NDAD and AD brains that may establish a degenerative link between the two cohorts, in addition to NDAD specific transcriptomic changes. These findings pinpoint novel targets for developing earlier diagnostics and preventative therapies for AD prior to diagnosis of probable AD. We also provide this high-quality, low post-mortem interval (PMI), cell-specific, and region-specific NDAD/AD reference data set to the community as a public resource.

Original languageEnglish
Pages (from-to)549-566
Number of pages18
JournalNeurobiology of Aging
Volume31
Issue number4
DOIs
StatePublished - Apr 2010

Keywords

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

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    Liang, W. S., Dunckley, T., Beach, T. G., Grover, A., Mastroeni, D., Ramsey, K., Caselli, R. J., Kukull, W. A., McKeel, D., Morris, J. C., Hulette, C. M., Schmechel, D., Reiman, E. M., Rogers, J., & Stephan, D. A. (2010). Neuronal gene expression in non-demented individuals with intermediate Alzheimer's Disease neuropathology. Neurobiology of Aging, 31(4), 549-566. https://doi.org/10.1016/j.neurobiolaging.2008.05.013