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The Expression of Transthyretin and Amyloid-beta Protein Precursor is Altered in the Brain of Idiopathic Normal Pressure Hydrocephalus Patients
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..
Univ Turku, Inst Biomed, Turku, Finland..
Univ Gothenburg, Sahlgrenska Acad, Clin Neurochem Lab, Dept Psychiat & Neurochem, Gothenburg, Sweden..
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2015 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 48, no 4, 959-968 p.Article in journal (Refereed) PublishedText
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. Vol. 48, no 4, 959-968 p.
Keyword [en]
Alzheimer's disease, amyloid-beta protein precursor, gene expression profiling, idiopathic normal pressure hydrocephalus, transthyretin
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URN: urn:nbn:se:uu:diva-268725DOI: 10.3233/JAD-150268ISI: 000363867300008PubMedID: 26444765OAI: oai:DiVA.org:uu-268725DiVA: diva2:878769

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Available from: 2015-12-09 Created: 2015-12-09 Last updated: 2015-12-09Bibliographically approved

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