Binding of amyloid beta precursor protein to coagulation factor XIa in vivo may favour haemorrhagic stroke
| Autor: | Van Nostrand We, Meijers Jc, Joost Haan, Ross Ra, von dem Borne Pa, Bornebroek M |
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| Přispěvatelé: | Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Adult
Male medicine.medical_specialty Pathology Amyloid Enzyme-Linked Immunosorbent Assay Factor XIa Pathogenesis Amyloid beta-Protein Precursor Cerebral circulation In vivo Internal medicine Blood plasma medicine Amyloid precursor protein Humans Platelet Prospective Studies Aged Cerebral Hemorrhage biology Chemistry Amyloidosis Middle Aged medicine.disease Endocrinology Neurology Case-Control Studies biology.protein Female Neurology (clinical) Protein Binding |
| Zdroj: | Journal of neurology, 245(2), 111-115. D. Steinkopff-Verlag |
| ISSN: | 0340-5354 |
| DOI: | 10.1007/s004150050188 |
| Popis: | Hereditary cerebral haemorrhage with amyloidosis, Dutch type (HCHWA-D), caused by a mutation at codon 693 in the amyloid β precursor protein (βPP) gene, is clinically characterised by haemorrhagic strokes and dementia. The secreted forms βPP751 and βPP770 are identical to protease nexin II (PNII), which is a potent inhibitor of intrinsic blood coagulation factor XIa in vitro. We investigated the concentration of complexes between factor XIa and βPP in vivo, to search for a possible cause of the haemorrhagic strokes in HCHWA-D. In this prospectively designed study, first an enzyme-linked immunosorbent assay (ELISA) was performed with dilutions of the factor XIa-βPP complexes prepared from platelets as a standard curve. By means of this ELISA, the concentration of factor XIa-βPP complexes was measured in plasma samples. Second, plasma of 23 HCHWA-D patients and 23 healthy controls was collected, and the concentration of complexes was measured with this method. The mean concentration of factor XIa-βPP complexes in plasma of HCHWA-D patients (mean 13.73 U/ ml; SD 4.78) was significantly (P = 0.05) higher than the concentration in plasma of healthy controls (mean 11.37; SD 2.77). The differences, however, were small and there was a major overlap between the concentrations in patients and controls. In HCHWA-D mutation carriers, the concentration of factor XIa-βPP complexes was not related to age, and there was no difference between presymptomatic and symptomatic mutation carriers. From this study, it can be concluded that βPP forms complexes with factor XIa in vivo both in HCHWA-D patients and in normal controls. The concentration in HCHWA-D patients was higher. This is probably the result of diffusion of complexes from the cerebral circulation into plasma. Elevated βPP in cerebrovascular amyloid deposits is possibly a local factor contributing to the development of haemorrhagic strokes. |
| Databáze: | OpenAIRE |
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