title: ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations.
abstract: Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer's disease (AD). Although possession of E2 is protective in the context of AD, E2 appears to confer an increased incidence and severity of posttraumatic stress disorder (PTSD). However, the biological processes underlying this link remain unclear. In this study, we began to elucidate these associations by examining the effects of apoE on PTSD severity in combat veterans, and on PTSD-like behavior in mice with human apoE. In a group of 92 veterans with PTSD, we observed significantly higher Clinician-Administered PTSD Scale and PTSD Checklist scores in E2+ individuals, as well as alterations in salivary cortisol levels. Furthermore, we measured behavioral and biological outcomes in mice expressing human apoE after a single stressful event as well as following a period of chronic variable stress, a model of combat-related trauma. Mice with E2 showed impairments in fear extinction, and behavioral, cognitive, and neuroendocrine alterations following trauma. To the best of our knowledge, these data constitute the first translational demonstration of PTSD severity in men and PTSD-like symptoms in mice with E2, and point to apoE as a novel biomarker of susceptibility, and potential therapeutic target, for PTSD.
authors: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA.
authors: Lance A
authors: LA
authors: Johnson
authors: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA.
authors: Damian G
authors: DG
authors: Zuloaga
authors: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA.
authors: Erin
authors: E
authors: Bidiman
authors: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA.
authors: Tessa
authors: T
authors: Marzulla
authors: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA.
authors: Sydney
authors: S
authors: Weber
authors: Department of Neurology, Oregon Health and Science University, Portland, OR, USA.
authors: Helane
authors: H
authors: Wahbeh
authors: 1] Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA [2] Department of Neurology, Oregon Health and Science University, Portland, OR, USA [3] Department of Radiation Medicine and Division of Neuroscience, ONPRC, Oregon Health and Science University, Beaverton, OR, USA.
authors: Jacob
authors: J
authors: Raber
mesh_terms: D000203:Activities of Daily Living; D000818:Animals; D053329:Apolipoprotein E2 / Q000235:genetics* / Q000378:metabolism; D021081:Chronobiology Disorders / Q000235:genetics; D003071:Cognition / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism*; D004195:Disease Models, Animal; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008569:Memory Disorders / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D012463:Saliva / Q000378:metabolism; D013313:Stress Disorders, Post-Traumatic / Q000150:complications / Q000235:genetics* / Q000523:psychology*; D014728:Veterans
chemical_list: D053329:Apolipoprotein E2; D003345:Corticosterone; D006854:Hydrocortisone