title: The Expression of Transthyretin and Amyloid-β Protein Precursor is Altered in the Brain of Idiopathic Normal Pressure Hydrocephalus Patients.
abstract: BACKGROUND
  Idiopathic normal pressure hydrocephalus (iNPH) is a dementing condition in which Alzheimer's disease (AD)-related amyloid-β (Aβ) plaques are frequently observed in the neocortex. iNPH patients with prominent Aβ pathology show AD-related alterations in amyloid-β protein precursor (AβPP) processing resulting from increased γ-secretase activity.
  
  
  OBJECTIVE
  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 ~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 sAβPPα, sAβPPβ, 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 βPP 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 βPP was on average three times higher in iNPH samples as compared to control samples. Interestingly, the expression of α-secretase (ADAM10) was also increased in iNPH patients. In the lumbar CSF samples, soluble TTR levels showed a significant positive correlation with sAβPPα and sAβPPβ, 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.
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.|Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland and Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Laiterä
authors.affiliation: Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland and Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Mitja I
authors.initials: MI
authors.lastname: Kurki
authors.affiliation: Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Juha-Pekka
authors.initials: JP
authors.lastname: Pursiheimo
authors.affiliation: Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Helisalmi
authors.affiliation: Institute of Clinical Medicine - Pathology, University of Eastern Finland and Department of Pathology, Kuopio University Hospital, Kuopio, Finland.|Department of Pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Tuomas
authors.initials: T
authors.lastname: Rauramaa
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Remes
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.|Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, Kuopio, Finland.
authors.forename: Annakaisa
authors.initials: A
authors.lastname: Haapasalo
authors.affiliation: Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland and Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Juha E
authors.initials: JE
authors.lastname: Jääskeläinen
authors.affiliation: Institute of Clinical Medicine - Neurology, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.|Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Hiltunen
authors.affiliation: Institute of Clinical Medicine - Neurosurgery, University of Eastern Finland and Neurosurgery of NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Leinonen
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D000368:Aged; D000369:Aged, 80 and over; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D011228:Prealbumin / Q000378:metabolism*; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000378:metabolism; D013129:Spinal Puncture
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D008565:Membrane Proteins; D011228:Prealbumin; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human
keywords: Alzheimer’s disease; amyloid-β protein precursor; gene expression profiling; idiopathic normal pressure hydrocephalus; transthyretin