1. Neuronal gene expression in non-demented individuals with intermediate Alzheimer's Disease neuropathology.
- Author
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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, and Stephan DA
- Subjects
- Aged, 80 and over, Alzheimer Disease physiopathology, Brain metabolism, Brain physiopathology, Cohort Studies, Databases, Genetic, Disease Progression, Female, Humans, Male, Microdissection methods, Nerve Tissue Proteins genetics, Neurons metabolism, Oligonucleotide Array Sequence Analysis, Plaque, Amyloid genetics, Plaque, Amyloid metabolism, Predictive Value of Tests, Proteasome Endopeptidase Complex genetics, Proteasome Endopeptidase Complex metabolism, RNA, Messenger analysis, RNA, Messenger metabolism, Reference Standards, Reverse Transcriptase Polymerase Chain Reaction, Synapses metabolism, Synapses pathology, Alzheimer Disease genetics, Alzheimer Disease pathology, Brain pathology, Gene Expression Profiling methods, Gene Expression Regulation physiology, Neurons pathology
- 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., (Copyright (c) 2008 Elsevier Inc. All rights reserved.)
- Published
- 2010
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