APOE Is Associated With Serum Tau Following Uncomplicated Mild Traumatic Brain Injury

Sara M Lippa; Rael T Lange; Clifton L Dalgard; Anthony R Soltis; Vivian A Guedes; Tracey A Brickell; Louis M French; Jessica Gill

doi:10.3389/fneur.2022.816625

APOE Is Associated With Serum Tau Following Uncomplicated Mild Traumatic Brain Injury

Front Neurol. 2022 Jul 14:13:816625. doi: 10.3389/fneur.2022.816625. eCollection 2022.

Authors

Sara M Lippa¹, Rael T Lange^{1

2

3

4

5}, Clifton L Dalgard^{6

7}, Anthony R Soltis^{8

9}, Vivian A Guedes⁸, Tracey A Brickell^{1

2

4

5

6}, Louis M French^{1

2

6}, Jessica Gill^{10

11

12}

Affiliations

¹ National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, United States.
² Department of Research, Tramatic Brain Injury Center of Excellence, Silver Spring, MD, United States.
³ Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
⁴ Centre of Excellence on Post-traumatic Stress Disorder, Ottawa, ON, Canada.
⁵ General Dynamics Information Technology, Falls Church, VA, United States.
⁶ Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
⁷ The American Genome Center, Bethesda, MD, United States.
⁸ Henry M. Jackson Foundation, Bethesda, MD, United States.
⁹ PRIMER, Bethesda, MD, United States.
¹⁰ Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, United States.
¹¹ School of Nursing, Johns Hopkins University, Baltimore, MD, United States.
¹² Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, United States.

Abstract

Background and objectives: APOE e4 has been linked to poor outcome following traumatic brain injury (TBI); however, the mechanisms behind this relationship are unclear. Few studies have investigated the relationship between the APOE genotype and established brain related protein biomarkers following TBI. The purpose of this study was to examine this relationship in service members and veterans (SMVs) following TBI.

Methods: Participants were 209 SMVs [124 uncomplicated mild TBI (mTBI); 85 complicated mild, moderate, severe, or penetrating TBI (mod-sev TBI)] prospectively enrolled in the DVBIC-TBICoE 15-Year Longitudinal TBI Study. APOE genotyping was undertaken using non-fasting blood serum samples. Participants were divided into three groups: APOE e2+, APOE e3/e3, and APOE e4+.

Results: In participants with mTBI, those with the APOE e2 allele had significantly lower levels of tau than those with APOE e4 (p = 0.005, r = 0.43, medium-large effect size). Those with APOE e3/e3 trended toward having higher tau than those APOE e2+ (p = 0.076, r = 0.20, small-medium effect size) and lower tau than those with APOE e4+ (p = 0.062, r = 0.21, small-medium effect size). There were no significant differences in biomarkers based on APOE in the mod-sev TBI group.

Discussion: This study is the first to demonstrate APOE genotype is related to serum tau levels following a mTBI, extending prior findings to human serum following mTBI. In addition to higher serum tau levels in APOE e4 carriers, lower tau levels were observed in APOE e2 carriers, suggesting a possible protective effect.

Keywords: APOE; biomarkers; military; serum; tau; traumatic brain injury.