title: APP mRNA splicing is upregulated in the brain of biglycan transgenic mice.
abstract: Many of the risk factors for cerebrovascular disease and atherosclerosis also increase the risk of Alzheimer's disease, characterized by the cerebral deposition of beta-amyloid plaques resulting from the abnormal processing of the transmembrane amyloid precursor protein (APP). The initiating event of cholesterol-induced atherosclerosis is the retention and accumulation of atherogenic apolipoprotein B (apoB) together with low-density lipoproteins in the vascular intima. Biglycan, a member of the small leucine-rich protein family, was suspected of contributing to this process. The individual and combined overexpressions of biglycan and apoB-100 were therefore examined on the cortical APP mRNA levels of transgenic mice by means of semiquantitative PCR. As compared with the control littermates, transgenic biglycan mice had significantly increased cortical APP695 (122%) and APP770 (157%) mRNA levels, while the double transgenic (apoB(+/-)xbiglycan(+/-)) mice did not exhibit any changes. These results provide the first experimental evidence that the atherogenic risk factor biglycan alters APP splicing and may participate in the pathogenesis of both Alzheimer and vascular dementias.
authors.affiliation: Alzheimer's Disease Research Centre, Department of Psychiatry, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, University of Szeged, 6 Semmelweis u., Szeged H-6725, Hungary. a_bjelik@yahoo.com
authors.forename: Annamária
authors.initials: A
authors.lastname: Bjelik
authors.forename: Magdolna
authors.initials: M
authors.lastname: Pákáski
authors.forename: Erika
authors.initials: E
authors.lastname: Bereczki
authors.forename: Szilvia
authors.initials: S
authors.lastname: Gonda
authors.forename: Anna
authors.initials: A
authors.lastname: Juhász
authors.forename: Agnes
authors.initials: A
authors.lastname: Rimanóczy
authors.forename: Marianna
authors.initials: M
authors.lastname: Zana
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Janka
authors.forename: Miklós
authors.initials: M
authors.lastname: Sántha
authors.forename: János
authors.initials: J
authors.lastname: Kálmán
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D058578:Biglycan; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016564:Amyloid beta-Protein Precursor; C546885:Bgn protein, mouse; D058578:Biglycan; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger