Complement protein levels in plasma astrocyte-derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia

Charisse N Winston; Edward J Goetzl; Janice B Schwartz; Fanny M Elahi; Robert A Rissman

doi:10.1016/j.dadm.2018.11.002

Complement protein levels in plasma astrocyte-derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia

Alzheimers Dement (Amst). 2019 Jan 9:11:61-66. doi: 10.1016/j.dadm.2018.11.002. eCollection 2019 Dec.

Authors

Charisse N Winston¹, Edward J Goetzl^{2

3}, Janice B Schwartz^{2

3

4}, Fanny M Elahi⁵, Robert A Rissman¹

Affiliations

¹ Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
² Jewish Home of San Francisco, San Francisco, CA, USA.
³ Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
⁴ Department of Bioengineering, University of California, San Francisco, San Francisco, CA, USA.
⁵ Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.

Abstract

Introduction: Levels of complement proteins (CPs) in plasma astrocyte-derived exosomes (ADEs) that are abnormal in Alzheimer's disease (AD) have not been assessed in mild cognitive impairment (MCI).

Methods: Participants (n = 20 per group) had either MCI converting to dementia within 3 years (MCIC), MCI remaining stable over 3 years (MCIS), Alzheimer's disease, or were controls. CPs of ADEs isolated from plasmas by anti-human glutamine aspartate transporter antibody absorption were quantified by ELISAs.

Results: ADE levels of C1q and C4b of the classical pathway, factor D and fragment Bb of the alternative pathway, and C5b, C3b, and C5b-C9 of both pathways were significantly higher in patients with MCIC than those with MCIS. ADE levels of inhibitory CPs decay-accelerating factor, CD46, CD59, and type 1 complement receptor were significantly lower in patients with MCIC than those with MCIS.

Discussion: ADE CPs are components of neurotoxic neuroinflammation that may be predictive biomarkers of MCI conversion to Alzheimer's disease.

Keywords: Biomarkers; Cognitive loss; Complement regulators; Neurodegeneration; Neuroinflammation.

Abstract

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