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.
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.
Authors: Young Ho Park; Angela Hodges; Shannon L Risacher; Kuang Lin; Jae-Won Jang; Soyeon Ahn; SangYun Kim; Simon Lovestone; Andrew Simmons; Michael W Weiner; Andrew J Saykin; Kwangsik Nho Journal: Neurobiol Aging Date: 2019-12-10 Impact factor: 4.673
Authors: Shweta Bagewadi; Subash Adhikari; Anjani Dhrangadhariya; Afroza Khanam Irin; Christian Ebeling; Aishwarya Alex Namasivayam; Matthew Page; Martin Hofmann-Apitius; Philipp Senger Journal: Database (Oxford) Date: 2015-10-16 Impact factor: 3.451
Authors: Sanjana Sood; Iain J Gallagher; Katie Lunnon; Eric Rullman; Aoife Keohane; Hannah Crossland; Bethan E Phillips; Tommy Cederholm; Thomas Jensen; Luc J C van Loon; Lars Lannfelt; William E Kraus; Philip J Atherton; Robert Howard; Thomas Gustafsson; Angela Hodges; James A Timmons Journal: Genome Biol Date: 2015-09-07 Impact factor: 13.583