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Alzheimer’s disease: neurofibrillary tangles (Rogers-3U24NS043571-01S1)

ABSTRACT: Alzheimer's Disease (AD) is a devastating neurodegenerative disorder affecting approximately 4 million people in the U.S. alone. AD is characterized by the presence of senile plaques and neurofibrillary tangles in cortical regions of the brain. These pathological markers are thought to be responsible for the massive cortical neurodegeneration and concomitant loss of memory, reasoning, and often aberrant behaviors that are seen in patients with AD. Understanding the molecular mechanisms whereby these histopathological markers develop will greatly enhance our understanding of AD development and progression. A clearer understanding of the mechanisms underlying neurofibrillary tangle formation specifically may help to clarify the basis for dementia of AD as well as the dementias associated with other diseases that are collectively referred to as "tauopathies." To expression profile both neurons containing neurofibrillary tangles and normal neurons from the entorhinal cortex of 10 mid-stage AD cases. The gene expression profile of neurons that contain neurofibrillary tangles will differ from the expression profile of histopathologically normal neurons from the same patient and from the same brain region. Some of these differences will be informative as to the mechanisms of tangle formation. Keywords: disease-state analysis

ORGANISM(S): Homo sapiens

PROVIDER: GSE4757 | GEO | 2006/05/02

SECONDARY ACCESSION(S): PRJNA95567

REPOSITORIES: GEO

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Project description:Alzheimer's Disease (AD) is a devastating neurodegenerative disorder affecting approximately 4 million people in the U.S. alone. AD is characterized by the presence of senile plaques and neurofibrillary tangles in cortical regions of the brain. These pathological markers are thought to be responsible for the massive cortical neurodegeneration and concomitant loss of memory, reasoning, and often aberrant behaviors that are seen in patients with AD. Understanding the molecular mechanisms whereby these histopathological markers develop will greatly enhance our understanding of AD development and progression. A clearer understanding of the mechanisms underlying neurofibrillary tangle formation specifically may help to clarify the basis for dementia of AD as well as the dementias associated with other diseases that are collectively referred to as "tauopathies."; To expression profile both neurons containing neurofibrillary tangles and normal neurons from the entorhinal cortex of 10 mid-stage AD cases. The gene expression profile of neurons that contain neurofibrillary tangles will differ from the expression profile of histopathologically normal neurons from the same patient and from the same brain region. Some of these differences will be informative as to the mechanisms of tangle formation. Experiment Overall Design: First use laser capture microdissection to select 1000 neurons bearing neurofibrillary tangles and 1000 normal neurons from the layer 2 stellate island neurons of the entorhinal cortex of 10 mid-stage AD cases. Second, to isolate the RNA from these captured neurons, perform double round linear amplification and hybridize the labeled cRNA to affymetrix U133A arrays. Third, to use paired, permutational t-tests to analyze the microarray data to select tangle-specific differences in gene expression. For the purposes of submitting this proposal, a value of 1 ug of RNA was entered due to web site constraints on values placed in that field. However, all samples are from LCM captured cells and the actual RNA yield is likely closer to 100 pg.

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Alzheimer’s disease: neurofibrillary tangles (Rogers-3U24NS043571-01S1)

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