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Transcriptional vulnerability of brain regions in Alzheimer's disease and dementia.

Neurobiology of aging | 2009

This study determined (a) the association between stages of Alzheimer's disease (AD) and overall gene expression change, and (b) brain regions of greatest vulnerability to transcriptional change as the disease progressed. Fifteen cerebrocortical sites and the hippocampus were examined in persons with either no cognitive impairment or neuropathology, or with only AD-associated lesions. Cases were stratified into groups of 7-19 based on the degree of cognitive impairment (clinical dementia rating scale, CDR); neurofibrillary tangle distribution and severity (Braak staging) or density of cerebrocortical neuritic plaque (NP; grouping by NP density). Transcriptional change was assessed by Affymetrix U133 mRNA microarray analysis. The results suggested that (a) gene expression changes in the temporal and prefrontal cortices are more closely related to disease severity than other regions examined; (b) more genes are down-regulated at any given disease severity stage than up-regulated; (c) the degree of gene expression change in a given regions depends on the disease severity classification scheme used; and (d) the classification of cases by CDR provides a more orderly gradient of gene expression change in most brain regions than Braak staging or NP grouping.

Pubmed ID: 17845826 RIS Download

Research resources used in this publication

None found

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Associated grants

  • Agency: NIA NIH HHS, United States
    Id: P01 AG002219
  • Agency: NIA NIH HHS, United States
    Id: P01 AG002219-189002
  • Agency: NIA NIH HHS, United States
    Id: P01 AG002219-24A1
  • Agency: NIA NIH HHS, United States
    Id: AG02219

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CERAD - Consortium to Establish a Registry for Alzheimer's Disease (tool)

RRID:SCR_003016

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on January 4, 2023.Consortium that developed brief, standardized and reliable procedures for the evaluation and diagnosis of patients with Alzheimer's disease (AD) and other dementias of the elderly. These procedures included data forms, flipbooks, guidebooks, brochures, instruction manuals and demonstration tapes, which are now available for purchase. The CERAD assessment material can be used for research purposes as well as for patient care. CERAD has developed several basic standardized instruments, each consisting of brief forms designed to gather data on normal persons as well as on cognitively impaired or behaviorally disturbed individuals. Such data permit the identification of dementia based on clinical, neuropsychological, behavioral or neuropathological criteria. Staff at participating CERAD sites were trained and certified to administer the assessment instruments and to evaluate the subjects enrolled in the study. Cases and controls were evaluated at entry and annually thereafter including (when possible) autopsy examination of the brain to track the natural progression of AD and to obtain neuropathological confirmation of the clinical diagnosis. The CERAD database has become a major resource for research in Alzheimer's disease. It contains longitudinal data for periods as long as seven years on the natural progression of the disorder as well as information on clinical and neuropsychological changes and neuropathological manifestations.

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Agilent Technologies (tool)

RRID:SCR_013575

Company provides laboratories worldwide with analytical instruments and supplies, clinical and diagnostic testing services, consumables, applications and expertise in life sciences and applied chemical markets.

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