Posttraumatic stress disorder and total amyloid burden and amyloid-β 42/40 ratios in plasma: Results from a pilot study of World Trade Center responders

Richard Kew,Candace Stewart,Yael Deri,Erica Diminich,Mary Sano,Benjamin J Luft,Xiaohua Yang,Roman Kotov,Sean A.P Clouston,Evelyn J Bromet,Sam Gandy

doi:10.1016/j.dadm.2019.01.003

Abstract

IntroductionChronic posttraumatic stress disorder (PTSD) is associated with poor memory and increased burden of various degenerative cerebral neuropathologies. The goal of this pilot study was to determine whether PTSD was associated with changes in plasma-based neuropathological biomarkers of neurodegeneration among World Trade Center (WTC) responders. MethodsThirty-four WTC responders had blood drawn and flash-frozen within 15 minutes of retrieval. PTSD symptoms were assessed at that time. Age, sex, and WTC exposure duration were obtained from medical records. Plasma was assayed in duplicate using an ultra-sensitive single-molecule enzyme-linked immunosorbent assay to examine the distribution of amyloid-β (Aβ) 42/40 ratios, total Aβ, total tau, and neurofilament light (NfL). The comparison group was drawn from a bank of healthy controls collected and assayed at the same facility. ResultsThe average age of WTC responders at blood draw was 53 years. Half were PTSD positive (PTSD+) as indicated by symptom severity. WTC responders had lower Aβ42/Aβ40 ratios but higher total tau and NfL levels in the plasma than healthy controls. PTSD+ status was associated with lower plasma Aβ load and higher Aβ42/Aβ40 ratios. DiscussionFindings suggest that PTSD may be associated with alterations in plasma markers related to Aβ, tau, and NfL, highlighting the potential association between PTSD status and neurodegenerative neuropathology in WTC responders.

Highlights

Posttraumatic stress disorder and total amyloid burden and amyloid-b 42/40 ratios in plasma: Results from a pilot study of World Trade
These findings are suggestive of the presence of a degenerative neuropathological process causing brain changes, the only previous study that focused on discovery of possible associations between posttraumatic stress disorder (PTSD) and neuropathology used positron emission tomography to show that PTSD symptom severity was correlated with increased retention of an amyloid-binding ligand, presumably indicating increased Ab load [7]
Future directions: These findings suggest that future evaluation of plasma-based neuropathological biomarkers is warranted and support the use of positron emission tomography to determine whether altered plasma biomarkers of Alzheimer’s disease (AD)-related neuropathology occurring with chronic PTSD reflect an increased burden of Ab in the cerebral cortex as is evident in AD

Summary

Introduction

Posttraumatic stress disorder and total amyloid burden and amyloid-b 42/40 ratios in plasma: Results from a pilot study of World Trade. In vivo neuroimaging studies have revealed that chronic PTSD is associated with hippocampal volume loss and cortical thinning [5,6] These findings are suggestive of the presence of a degenerative neuropathological process causing brain changes, the only previous study that focused on discovery of possible associations between PTSD and neuropathology used positron emission tomography to show that PTSD symptom severity was correlated with increased retention of an amyloid-binding ligand, presumably indicating increased Ab load [7]. The goal of the present pilot study was to evaluate these associations by examining associations between PTSD symptom severity and plasma-based markers of Ab burden, total tau, and neurofilament light (NfL) in a sample of WTC responders

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Discussion

Conclusion