4.5 Article

Gene expression correlates of neurofibrillary tangles in Alzheimer's disease

Journal

NEUROBIOLOGY OF AGING
Volume 27, Issue 10, Pages 1359-1371

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2005.08.013

Keywords

Alzheimer's disease; neurofibrillary tangles; microarray; gene expression; dementia; neurodegeneration; NFT; laser capture microdissection

Funding

  1. NIA NIH HHS [K01 AG024079, P01 AG03991, K01 AG024079-02, AG05128, P30 AG19610, U01AG016976, R01 AG023193, P50 AG05681, P50 AG005128, P50 AG005681, 1-RO1-AG023193, P30 AG019610, K01 AG024079-01A2, P01 AG003991, U01 AG016976] Funding Source: Medline

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Neurofibrillary tangles (NFT) constitute one of the cardinal histopathological features of Alzheimer's disease (AD). To explore in vivo molecular processes involved in the development of NFTs, we compared gene expression profiles of NFT-bearing entorhinal cortex neurons from 19 AD patients, adjacent non-NFT-bearing entorhinal cortex neurons from the same patients, and non-NFT-bearing entorhinal cortex neurons from 14 non-demented, histopathologically normal controls (ND). Of the differentially expressed genes, 225 showed progressively increased expression (AD NFT neurons > AD non-NFT neurons > ND non-NFT neurons) or progressively decreased expression (AD NFT neurons < AD non-NFT neurons < ND non-NFT neurons), raising the possibility that they may be related to the early stages of NFT formation. Immunohistochemical studies confirmed that many of the implicated proteins are dysregulated and preferentially localized to NFTs, including apolipoprotein J, interleukin-1 receptor-associated kinase 1, tissue inhibitor of metalloproteinase 3, and casein kinase 2, beta. Functional validation studies are underway to determine which candidate genes may be causally related to NFT neuropathology, thus providing therapeutic targets for the treatment of AD. (c) 2005 Elsevier Inc. All rights reserved.

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