Gene expression correlates of neurofibrillary tangles in Alzheimer's disease.

Published

Journal Article

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.

Full Text

Cited Authors

  • Dunckley, T; Beach, TG; Ramsey, KE; Grover, A; Mastroeni, D; Walker, DG; LaFleur, BJ; Coon, KD; Brown, KM; Caselli, R; Kukull, W; Higdon, R; McKeel, D; Morris, JC; Hulette, C; Schmechel, D; Reiman, EM; Rogers, J; Stephan, DA

Published Date

  • October 2006

Published In

Volume / Issue

  • 27 / 10

Start / End Page

  • 1359 - 1371

PubMed ID

  • 16242812

Pubmed Central ID

  • 16242812

Electronic International Standard Serial Number (EISSN)

  • 1558-1497

Digital Object Identifier (DOI)

  • 10.1016/j.neurobiolaging.2005.08.013

Language

  • eng

Conference Location

  • United States