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

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 y...

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Main Authors: Charisse N. Winston, Edward J. Goetzl, Janice B. Schwartz, Fanny M. Elahi, Robert A. Rissman
Format: Article
Language:English
Published: Wiley 2019-12-01
Series:Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
Subjects:
Online Access:https://doi.org/10.1016/j.dadm.2018.11.002
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spelling doaj-f4487646af6b4c2e880ba353df3a3c572020-11-25T03:02:58ZengWileyAlzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring2352-87292019-12-01111616610.1016/j.dadm.2018.11.002Complement protein levels in plasma astrocyte‐derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementiaCharisse N. Winston0Edward J. Goetzl1Janice B. Schwartz2Fanny M. Elahi3Robert A. Rissman4Department of NeurosciencesUniversity of CaliforniaSan DiegoLa JollaCAUSAJewish Home of San FranciscoSan FranciscoCAUSAJewish Home of San FranciscoSan FranciscoCAUSADepartment of NeurologyUniversity of CaliforniaSan FranciscoSan FranciscoCAUSADepartment of NeurosciencesUniversity of CaliforniaSan DiegoLa JollaCAUSAAbstract 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.https://doi.org/10.1016/j.dadm.2018.11.002NeuroinflammationNeurodegenerationBiomarkersCognitive lossComplement regulators
collection DOAJ
language English
format Article
sources DOAJ
author Charisse N. Winston
Edward J. Goetzl
Janice B. Schwartz
Fanny M. Elahi
Robert A. Rissman
spellingShingle Charisse N. Winston
Edward J. Goetzl
Janice B. Schwartz
Fanny M. Elahi
Robert A. Rissman
Complement protein levels in plasma astrocyte‐derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia
Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
Neuroinflammation
Neurodegeneration
Biomarkers
Cognitive loss
Complement regulators
author_facet Charisse N. Winston
Edward J. Goetzl
Janice B. Schwartz
Fanny M. Elahi
Robert A. Rissman
author_sort Charisse N. Winston
title Complement protein levels in plasma astrocyte‐derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia
title_short Complement protein levels in plasma astrocyte‐derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia
title_full Complement protein levels in plasma astrocyte‐derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia
title_fullStr Complement protein levels in plasma astrocyte‐derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia
title_full_unstemmed Complement protein levels in plasma astrocyte‐derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia
title_sort complement protein levels in plasma astrocyte‐derived exosomes are abnormal in conversion from mild cognitive impairment to alzheimer's disease dementia
publisher Wiley
series Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
issn 2352-8729
publishDate 2019-12-01
description 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.
topic Neuroinflammation
Neurodegeneration
Biomarkers
Cognitive loss
Complement regulators
url https://doi.org/10.1016/j.dadm.2018.11.002
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