title: Prediction of mild cognitive impairment that evolves into Alzheimer's disease dementia within two years using a gene expression signature in blood: a pilot study.
abstract: BACKGROUND
  The focus on Alzheimer's disease (AD) is shifting from dementia to the prodromal stage of the disorder, to a large extent due to increasing efforts in trying to develop disease modifying treatment for the disorder. For development of disease-modifying drugs, a reliable and accurate test for identification of mild cognitive impairment (MCI) due to AD is essential.
  
  
  OBJECTIVE
  In the present study, MCI progressing to AD will be predicted using blood-based gene expression.
  
  
  METHODS
  Gene expression analysis using qPCR was performed on blood RNA from a cohort of patients with amnestic MCI (aMCI; n = 66). Within the aMCI cohort, patients progressing to AD within 1 to 2 years were grouped as MCI converters (n = 34) and the patients remaining at the MCI stage after 2 years were grouped as stable MCI (n = 32). AD and control populations were also included in the study.
  
  
  RESULTS
  Multivariate statistical method partial least square regression was used to develop predictive models which later were tested using leave-one-out cross validation. Gene expression signatures that identified aMCI subjects that progressed to AD within 2 years with a prediction accuracy of 74%-77% were identified for the complete dataset and subsets thereof.
  
  
  CONCLUSIONS
  The present pilot study demonstrates for the first time that MCI that evolves into AD dementia within 2 years may be predicted by analyzing gene expression in blood. Further studies will be needed to validate this gene signature as a potential test for AD in the predementia stage.
authors.affiliation: DiaGenic ASA, Grenseveien 92, Oslo, Norway. line.roed@diagenic.com
authors.forename: Line
authors.initials: L
authors.lastname: Roed
authors.forename: Gisle
authors.initials: G
authors.lastname: Grave
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Lindahl
authors.forename: Edith
authors.initials: E
authors.lastname: Rian
authors.forename: Peter O
authors.initials: PO
authors.lastname: Horndalsveen
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
authors.forename: Christer
authors.initials: C
authors.lastname: Nilsson
authors.forename: Frank
authors.initials: F
authors.lastname: Swenson
authors.forename: Anders
authors.initials: A
authors.lastname: Lönneborg
authors.forename: Praveen
authors.initials: P
authors.lastname: Sharma
authors.forename: Magnus
authors.initials: M
authors.lastname: Sjögren
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D015999:Multivariate Analysis; D010865:Pilot Projects; D011237:Predictive Value of Tests; D012313:RNA / Q000097:blood* / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics*
chemical_list: D012313:RNA