title: Differential Expression of microRNA in Cerebrospinal Fluid as a Potential Novel Biomarker for Alzheimer's Disease.
abstract: OBJECTIVE
  The need to find a better reflection of Alzheimer's disease (AD) pathophysiology led us to investigate differential expression of microRNA (miRNA) in cerebrospinal fluid (CSF) of AD patients compared to matched controls, using a genome-wide data-driven approach.
  
  
  METHODS
  From the Amsterdam Dementia Cohort, we selected 19 AD patients with CSF indicative of AD pathophysiology and 19 age and gender-matched controls without CSF evidence of AD (67 ± 6 years old, 20 [53%] female). We measured 754 miRNA in CSF using qRT-PCR (Taqman Array MicroRNA cards A and B, v3.0) according to the Megaplex Taqman protocol. Hierarchical cluster analysis was performed and groups were compared using Linear Models for Microarray Data, a modified t-test. We performed validation analysis using qRT-PCR single assays.
  
  
  RESULTS
  144 ± 66 miRNA could be detected using Megaplex array analysis (19% ). Mean Ct (average 32.4 ± 0.5) was correlated to age (r = 0.52, p = 0.001). Five miRNA were differentially expressed in CSF of AD patients. None of these could be replicated. After stratification by age, seven miRNA showed differential expression in late-onset AD, of which lower abundance of let-7a was replicated (log10RQ -1.46, p <  0.05). In early-onset AD, twelve miRNA were differentially expressed of which lower abundance of miRNA-532-3p remained borderline significant (log10RQ -1.27, p = 0.05).
  
  
  CONCLUSIONS
  Although we could not consistently separate AD patients and controls in the whole group, we have found indications miRNA in CSF are able to reflect aging and perhaps also heterogeneity in AD. Further investigation requires optimizing RNA input, while maintaining strict age matching.
authors.affiliation: Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands.|Departments of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Argonde C
authors.initials: AC
authors.lastname: van Harten
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Joyce
authors.initials: J
authors.lastname: Mulders
authors.affiliation: Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands.|Departments of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands.|Departments of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.|Department of Epidemiology/Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Cees B M
authors.initials: CB
authors.lastname: Oudejans
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000134:cerebrospinal fluid* / Q000235:genetics; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012333:RNA, Messenger / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Alzheimer’s disease; biomarkers; cerebrospinal fluid; microRNAs