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
2013 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, Vol. 35, no 3, 611-621 p.Article in journal (Refereed) Published
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. Material and 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. Conclusion: 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.
Place, publisher, year, edition, pages
2013. Vol. 35, no 3, 611-621 p.
Alzheimer's disease, biomarkers, diagnostic tests, gene expression signatures, mild cognitive impairment
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-201889DOI: 10.3233/JAD-122404ISI: 000318627800017OAI: oai:DiVA.org:uu-201889DiVA: diva2:629681