Park, YH;
Hodges, A;
Simmons, A;
Lovestone, S;
Weiner, MW;
Kim, SY;
Saykin, AJ;
... Hsiao, J; + view all
(2020)
Association of blood-based transcriptional risk scores with biomarkers for Alzheimer disease.
Neurology: Genetics
, 6
(6)
, Article e517. 10.1212/NXG.0000000000000517.
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Abstract
Objective: To determine whether transcriptional risk scores (TRSs), a summation of polarized expression levels of functional genes, reflect the risk of Alzheimer disease (AD). / Methods: Blood transcriptome data were from Caucasian participants, which included AD, mild cognitive impairment, and cognitively normal controls (CN) in the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 661) and AddNeuroMed (n = 674) cohorts. To calculate TRSs, we selected functional genes that were expressed under the control of the AD risk loci and were identified as being responsible for AD by using Bayesian colocalization and mendelian randomization methods. Regression was used to investigate the association of the TRS with diagnosis (AD vs CN) and MRI biomarkers (entorhinal thickness and hippocampal volume). Regression was also used to evaluate whether expression of each functional gene was associated with AD diagnosis. / Results: The TRS was significantly associated with AD diagnosis, hippocampal volume, and entorhinal cortical thickness in the ADNI. The association of the TRS with AD diagnosis and entorhinal cortical thickness was also replicated in AddNeuroMed. Among functional genes identified to calculate the TRS, CD33 and PILRA were significantly upregulated, and TRAPPC6A was significantly downregulated in patients with AD compared with CN, all of which were identified in the ADNI and replicated in AddNeuroMed. / Conclusions: The blood-based TRS is significantly associated with AD diagnosis and neuroimaging biomarkers. In blood, CD33 and PILRA were known to be associated with uptake of β-amyloid and herpes simplex virus 1 infection, respectively, both of which may play a role in the pathogenesis of AD. / Classification of evidence: The study is rated Class III because of the case control design and the risk of spectrum bias.
| Type: | Article |
|---|---|
| Title: | Association of blood-based transcriptional risk scores with biomarkers for Alzheimer disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1212/NXG.0000000000000517 |
| Publisher version: | https://doi.org/10.1212/NXG.0000000000000517 |
| Language: | English |
| Additional information: | Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
| Keywords: | Alzheimer's disease, Gene expression studies |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10117739 |
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