title: Changes in signal transduction in Alzheimer's disease.
abstract: We studied the signal transduction system including the receptor and protein kinase C (PKC) in Alzheimer's disease (AD) brains. We used 3H-TCP as a ligand for the NMDA receptor-ion channel complex. The total concentrations of 3H-TCP binding sites were significantly reduced in AD frontal cortex. 3H-TCP binding sites spared in AD brains retained the affinity for the ligand and the reactivity to NMDA, L-glutamate, and glycine. We utilized antibodies to assess the degree of involvement of different PKC isoforms in AD. The concentration of PKC (beta II) was lower in AD particulate fractions and higher in AD cytosol fractions. Immunocytochemical studies revealed reduced numbers of anti-PKC (beta II)-immunopositive neurons. Anti-PKC (alpha) faintly stained entire plaques and surrounding glial cells. Anti-PKC (beta I) stained dystrophic plaque neurites. Anti-PKC (beta II) stained the amyloid-containing portions of plaques. These results suggest an involvement of second messenger cascades in the pathogenesis of AD in addition to neurotransmitters and their receptors.
authors.affiliation: Department of Neurology, Faculty of Medicine, Kyoto University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Shimohama
authors.forename: H
authors.initials: H
authors.lastname: Ninomiya
authors.forename: T
authors.initials: T
authors.lastname: Saitoh
authors.forename: R D
authors.initials: RD
authors.lastname: Terry
authors.forename: R
authors.initials: R
authors.lastname: Fukunaga
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: M
authors.initials: M
authors.lastname: Fujiwara
authors.forename: J
authors.initials: J
authors.lastname: Kimura
authors.forename: M
authors.initials: M
authors.lastname: Kameyama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007527:Isoenzymes; C012058:tenocyclidine; D011493:Protein Kinase C; D010622:Phencyclidine