APP mRNA splicing is upregulated in the brain of biglycan transgenic mice.
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.
Bjelik
Annamária
A
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
Pákáski
Magdolna
M
Bereczki
Erika
E
Gonda
Szilvia
S
Juhász
Anna
A
Rimanóczy
Agnes
A
Zana
Marianna
M
Janka
Zoltán
Z
Sántha
Miklós
M
Kálmán
János
J
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
D016564:Amyloid beta-Protein Precursor; C546885:Bgn protein, mouse; D058578:Biglycan; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger