Plasma Levels of Neuron- and Astrocyte-Derived Exosomal Amyloid Beta1-42, Amyloid Beta1-40, and Phosphorylated Tau Levels in Schizophrenia Patients and Non-psychiatric Comparison Subjects: Relationships With Cognitive Functioning and Psychopathology

Ellen E Lee; Charisse Winston-Gray; James W Barlow; Robert A Rissman; Dilip V Jeste

doi:10.3389/fpsyt.2020.532624

Plasma Levels of Neuron- and Astrocyte-Derived Exosomal Amyloid Beta1-42, Amyloid Beta1-40, and Phosphorylated Tau Levels in Schizophrenia Patients and Non-psychiatric Comparison Subjects: Relationships With Cognitive Functioning and Psychopathology

Front Psychiatry. 2021 Mar 2:11:532624. doi: 10.3389/fpsyt.2020.532624. eCollection 2020.

Authors

Ellen E Lee^{1

2}, Charisse Winston-Gray³, James W Barlow³, Robert A Rissman³, Dilip V Jeste⁴

Affiliations

¹ Department of Psychiatry, University of California San Diego, San Diego, CA, United States.
² Veterans Affairs San Diego Healthcare System, La Jolla, CA, United States.
³ Department of Neuroscience, University of California San Diego, San Diego, CA, United States.
⁴ Department of Psychiatry and Neurosciences, University of California San Diego, San Diego, CA, United States.

Abstract

Introduction: Cognitive deficits in people with schizophrenia (PWS) are a major predictor of disability and functioning, yet the underlying pathophysiology remains unclear. A possible role of amyloid and tau biomarkers (hallmarks of Alzheimer's disease) is still speculative in schizophrenia. Exosomes or extracellular vesicles, involved with cell-to-cell communication and waste removal, can be used to assay brain-based proteins from peripheral blood. To our knowledge, this is the first study of exosomal amyloid and tau protein levels in PWS. Methods: This cross-sectional study included 60 PWS and 60 age- and sex-comparable non-psychiatric comparison subjects (NCs), age range 26-65 years. Assessments of global cognitive screening, executive functioning, psychopathology, and physical measures were conducted. Exosomes were extracted and precipitated from fasting plasma and identified as neuron-derived exosomes (NDEs) or astrocyte-derived exosomes (ADEs). Human-specific ELISAs were used to assay levels of amyloid-beta 1-42 (Aβ42), amyloid-beta 1-40 (Aβ40), and phosphorylated T181 tau (P-T181-tau). Plasma assays for aging biomarkers (C-reactive protein and F2-isoprostanes) were also performed. Results: ADE-Aβ42 levels were higher in PWS compared to NCs, though the other exosomal markers were similar between the two groups. Higher ADE-P-T181-tau levels were associated with worse executive functioning. Among PWS, higher ADE-P-T181-tau levels were associated with less severe negative symptoms and increased F2-isoprostane levels. Astrocyte-derived Aβ marker levels were sensitive and specific in differentiating between diagnostic groups. Among PWS, Aβ40 levels differed most by exosomal origin. Discussion: Exosomal markers may provide novel insights into brain-based processes (e.g., aging, oxidative stress) from peripheral blood samples.

Keywords: astrocytes; cognition; executive functioning; neurodegenerative disease; neurons; serious mental illness.

Abstract

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