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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
- Roed, Line (author)
- Grave, Gisle (author)
- Lindahl, Torbjorn (author)
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- Rian, Edith (author)
- Horndalsveen, Peter O. (author)
- Swenson, Frank (author)
- Lonneborg, Anders (author)
- Sharma, Praveen (author)
- Sjogren, Magnus (author)
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- (creator_code:org_t)
- 2013
- 2013
- English.
- In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 35:3, s. 611-621
- Journal article (peer-reviewed)
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- Alzheimer's disease
- biomarkers
- diagnostic tests
- gene expression
- signatures
- mild cognitive impairment
- Alzheimer's disease
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- art (subject category)
- ref (subject category)
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- Uppsala University
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