title: Gene expression correlates of neurofibrillary tangles in Alzheimer's disease.
abstract: 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.
authors.affiliation: Neurogenomics Division, Translational Genomics Research Institute, 445 North 5th Street, Phoenix, AZ 85004, USA.
authors.forename: Travis
authors.initials: T
authors.lastname: Dunckley
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.forename: Keri E
authors.initials: KE
authors.lastname: Ramsey
authors.forename: Andrew
authors.initials: A
authors.lastname: Grover
authors.forename: Diego
authors.initials: D
authors.lastname: Mastroeni
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Walker
authors.forename: Bonnie J
authors.initials: BJ
authors.lastname: LaFleur
authors.forename: Keith D
authors.initials: KD
authors.lastname: Coon
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brown
authors.forename: Richard
authors.initials: R
authors.lastname: Caselli
authors.forename: Walter
authors.initials: W
authors.lastname: Kukull
authors.forename: Roger
authors.initials: R
authors.lastname: Higdon
authors.forename: Daniel
authors.initials: D
authors.lastname: McKeel
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Christine
authors.initials: C
authors.lastname: Hulette
authors.forename: Donald
authors.initials: D
authors.lastname: Schmechel
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.forename: Joseph
authors.initials: J
authors.lastname: Rogers
authors.forename: Dietrich A
authors.initials: DA
authors.lastname: Stephan
mesh_terms: D000369:Aged, 80 and over; D018728:Entorhinal Cortex / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins