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The Expression of T...
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Laitera, TiinaUniv Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.;Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.;Univ Eastern Finland, Inst Clin Med Neurosurg, Kuopio, Finland.;Kuopio Univ Hosp, Neurosurg NeuroCtr, SF-70210 Kuopio, Finland.
(author)
The Expression of Transthyretin and Amyloid-beta Protein Precursor is Altered in the Brain of Idiopathic Normal Pressure Hydrocephalus Patients
- Article/chapterEnglish2015
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LIBRIS-ID:oai:DiVA.org:uu-268725
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-268725URI
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https://doi.org/10.3233/JAD-150268DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Happasalo, Hiltunen och Leinonen bidrog i lika stor utsträckning till artikeln.
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Background: Idiopathic normal pressure hydrocephalus (iNPH) is a dementing condition in which Alzheimer's disease (AD)related amyloid-beta (A beta) plaques are frequently observed in the neocortex. iNPH patients with prominent A beta pathology show AD-related alterations in amyloid-beta protein precursor (A beta PP) processing resulting from increased gamma-secretase activity. Objectives: Our goal was to assess potential alterations in the global gene expression profile in the brain of iNPH patients as compared to non-demented controls and to evaluate the levels of the identified targets in the cerebrospinal fluid (CSF) of iNPH patients. Methods: The genome-wide expression profile of similar to 35,000 probes was assessed in the RNA samples obtained from 22 iNPH patients and eight non-demented control subjects using a microarray chip. The soluble levels of sA beta PP alpha, sA beta PP beta, and transthyretin (TTR) were measured from the CSF of 102 iNPH patients using ELISA. Results: After correcting the results for multiple testing, significant differences in the expression of TTR and A beta PP were observed between iNPH and control subjects. The mRNA levels of TTR were on average 17-fold lower in iNPH samples compared to control samples. Conversely, the expression level of A beta PP was on average three times higher in iNPH samples as compared to control samples. Interestingly, the expression of beta-secretase (ADAM10) was also increased in iNPH patients. In the lumbar CSF samples, soluble TTR levels showed a significant positive correlation with sA beta PP alpha and sA beta PP beta, but TTR levels did not predict the brain pathology or the shunt response. Conclusions: These findings suggest differences in the expression profile of key factors involved in AD-related cellular events in the brain of iNPH patients.
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Kurki, Mitja I.Univ Eastern Finland, Inst Clin Med Neurosurg, Kuopio, Finland.;Kuopio Univ Hosp, Neurosurg NeuroCtr, SF-70210 Kuopio, Finland.
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Pursiheimo, Juha-PekkaUniv Turku, Inst Biomed, Turku, Finland.
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Zetterberg, HenrikUniv Gothenburg, Sahlgrenska Acad, Clin Neurochem Lab, Dept Psychiat & Neurochem, Gothenburg, Sweden.
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Helisalmi, SeppoUniv Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.;Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.
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Rauramaa, TuomasUniv Eastern Finland, Inst Clin Med Pathol, Kuopio, Finland.;Kuopio Univ Hosp, Dept Pathol, SF-70210 Kuopio, Finland.
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Alafuzoff, IrinaUppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)irial548
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Remes, Anne M.Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.;Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.
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Soininen, HilkkaUniv Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.;Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.
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Haapasalo, AnnakaisaUniv Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.;Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.;AI Virtanen Inst Mol Sci, Dept Neurobiol, Kuopio, Finland.
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Jaaskelainen, Juha E.Univ Eastern Finland, Inst Clin Med Neurosurg, Kuopio, Finland.;Kuopio Univ Hosp, Neurosurg NeuroCtr, SF-70210 Kuopio, Finland.
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Hiltunen, MikkoUniv Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.;Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.;Univ Eastern Finland, Inst Biomed, Kuopio, Finland.
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Leinonen, VilleUniv Eastern Finland, Inst Clin Med Neurosurg, Kuopio, Finland.;Kuopio Univ Hosp, Neurosurg NeuroCtr, SF-70210 Kuopio, Finland.
(author)
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Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.;Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.;Univ Eastern Finland, Inst Clin Med Neurosurg, Kuopio, Finland.;Kuopio Univ Hosp, Neurosurg NeuroCtr, SF-70210 Kuopio, Finland.Univ Eastern Finland, Inst Clin Med Neurosurg, Kuopio, Finland.;Kuopio Univ Hosp, Neurosurg NeuroCtr, SF-70210 Kuopio, Finland.
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In:Journal of Alzheimer's Disease48:4, s. 959-9681387-28771875-8908
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Laitera, Tiina
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Helisalmi, Seppo
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Rauramaa, Tuomas
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Alafuzoff, Irina
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Remes, Anne M.
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Hiltunen, Mikko
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