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Titolo:
Intracellular accumulation of detergent-soluble amyloidogenic A beta fragment of Alzheimer's disease precursor protein in the hippocampus of aged transgenic mice
Autore:
Li, QX; Maynard, C; Cappai, R; McLean, CA; Cherny, RA; Lynch, T; Culvenor, JG; Trevaskis, J; Tanner, JE; Bailey, KA; Czech, C; Bush, AI; Beyreuther, K; Masters, CL;
Indirizzi:
Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia Univ Melbourne Parkville Vic Australia 3052 arkville, Vic 3052, Australia Mental Hlth Res Inst Victoria, Parkville, Vic, Australia Mental Hlth Res Inst Victoria Parkville Vic Australia le, Vic, Australia Univ Heidelberg, Ctr Mol Biol, D-6900 Heidelberg, Germany Univ HeidelbergHeidelberg Germany D-6900 ol, D-6900 Heidelberg, Germany Harvardt,niv, Massachusetts Gen Hosp, Sch Med, Lab Oxidat,Genet & Aging Uni Harvard Univ Charlestown MA USA p, Sch Med, Lab Oxidat,Genet & Aging Uni HarvardMAniv, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown,Harvard Univ Charlestown MA USA sp, Sch Med, Dept Psychiat, Charlestown,
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 6, volume: 72, anno: 1999,
pagine: 2479 - 2487
SICI:
0022-3042(199906)72:6<2479:IAODAA>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
C-TERMINAL FRAGMENT; CARBOXY-TERMINUS; HUMAN PLATELETS; FULL-LENGTH; PEPTIDE; EXPRESSION; BRAIN; RAT; NEUROTOXICITY; RECOGNITION;
Keywords:
Alzheimer's disease; amyloid beta-protein; amyloid precursor protein; C100; transgenic mouse; processing;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Masters, CL Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia Univ Melbourne Parkville Vic Australia 3052 c 3052, Australia
Citazione:
Q.X. Li et al., "Intracellular accumulation of detergent-soluble amyloidogenic A beta fragment of Alzheimer's disease precursor protein in the hippocampus of aged transgenic mice", J NEUROCHEM, 72(6), 1999, pp. 2479-2487

Abstract

To study amyloid beta-protein (A beta) production and aggregation in vivo,we created two transgenic (Tg) mouse lines expressing the C-terminal 100 amino acids of human amyloid precursor protein (APP): Tg C100.V717F and Tg C100,WT. Western blot analysis showed that human APP-C100 and A beta were produced in brain and some peripheral tissues and A beta was produced in serum. Using antibodies specific for the A beta C terminus we found that Tg C100.V717F produced a 1.6-fold increase in A beta 42/A beta 40 compared with Tg C100.WT. Approximately 30% of total brain A beta (similar to 122 ng/g of wet tissue) was water-soluble. The remaining 70% of A beta partitioned intothe particulate fraction and was completely sodium dodecyl sulfate-soluble, In contrast, human Alzheimer's disease brain has predominantly sodium dodecyl sulfate-insoluble A beta. Immunohistochemistry with an A beta(5-8) antibody showed that A beta or A beta-containing fragments accumulated intracellularly in the hippocampus of aged Tg C100.V717F mice. The soluble A beta levels in Tg brain are similar to those in normal human brain, and this mayexplain the lack of microscopic amyloid deposits in the Tg mice. However, this mouse model provides a system to study the intracellular processing and accumulation of A beta or A beta-containing fragments and to screen for compounds directed at the gamma-secretase activity.

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Documento generato il 20/09/20 alle ore 00:51:53