Plasma REST: a novel candidate biomarker of Alzheimer’s disease is modified by psychological intervention in an at-risk population

Ashton, N.J., Hye, A., Leckey, C.A., Jones, A.R., Elliott, C. , Wetherell, J.L., Lenze, E.J., Killick, R. and Marchant, N.L. (2017) Plasma REST: a novel candidate biomarker of Alzheimer’s disease is modified by psychological intervention in an at-risk population. Translational Psychiatry, 7, e1148. (doi: 10.1038/tp.2017.113) (PMID:28585932) (PMCID:PMC5537638)

Abstract

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain’s stress response. It is reduced in conditions of stress and Alzheimer’s disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention—mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit.

• Item Type: Articles
• Additional Information: This paper presents independent research funded by Alzheimer’s Research UK (ARUK-PPG-2015B-8), who also supports CL. NJA is funded by Butterfield Trust via Rosetree Trust UK. AH is funded by Research Centre for Mental Health and Biomedical Research Unit for Dementia. RK is funded by the Medical Research Council UK (MR/M013944/1). The Intervention study was funded by the National Center for Complementary and Integrative Health (NCCIH). NLM was supported by the Dementia Biomedical Research Unit at the South London and Maudsley NHS Foundation Trust, the Institute of Psychiatry, King’s College London, University College London, Alzheimer’s Society (AS-SF-15b-002) and the European Commission (667696).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Elliott, Dr Christina
• Authors: Ashton, N.J., Hye, A., Leckey, C.A., Jones, A.R., Elliott, C., Wetherell, J.L., Lenze, E.J., Killick, R., and Marchant, N.L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Translational Psychiatry
• Publisher: Springer Nature
• ISSN: 2158-3188
• ISSN (Online): 2158-3188
• Copyright Holders: Copyright © The Author(s) 2017
• First Published: First published in Translational Psychiatry 7:e1148
• Publisher Policy: Reproduced under a Creative Commons licence