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Cargo proteins of plasma astrocyte‐derived exosomes in Alzheimer's disease
Abstract
Efficient intercellular transfer of RNAs, proteins, and lipids as protected exosomal cargo has been demonstrated in the CNS, but distinct physiologic and pathologic roles have not been well defined for this pathway. The capacity to isolate immunochemically human plasma neuron‐derived exosomes (NDEs), containing neuronspecific cargo, has permitted characterization of CNS‐derived exosomes in living humans. Constituents of the amyloid β‐peptide (Aβ)42‐generating system now are examined in 2 distinct sets of human neural cells by quantification in astrocyte‐derived exosomes (ADEs) and NDEs, enriched separately from plasmas of patients with Alzheimer's disease (AD) or frontotemporal dementia (FTD) andmatched cognitively normal controls. ADE levels of β‐site amyloid precursor protein‐cleaving enzyme 1 (BACE‐1), γ‐secretase, soluble Aβ42, soluble amyloid precursor protein (sAPP)β, sAPPα, glial‐derived neurotrophic factor (GDNF), P‐T181‐tau, and P‐S396‐tau were significantly (3‐ to 20‐fold) higher than levels in NDEs for patients and controls. BACE‐1 levels also were a mean of 7‐fold higher in ADEs than in NDEs from cultured rat type‐specific neural cells. Levels of BACE‐1 and sAPPβ were significantly higher and of GDNF significantly lower in ADEs of patients with AD than in those of controls, but not significantly different in patients with FTD than in controls. Abundant proteins of the Aβ42 peptide‐generating system in ADEs may sustain levels in neurons. ADE cargo proteins may be useful for studies of mechanisms of cellular interactions and effects of BACE‐1 inhibitors in AD.—Goetzl, E. J., Mustapic, M., Kapogiannis, D., Eitan, E., Lobach, I. V., Goetzl, L., Schwartz, J. B., Miller, B. L. Cargo proteins of plasma astrocyte‐derived exosomes in Alzheimer's disease. FASEB J. 30, 3853–3859 (2016) www.fasebj.org
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EVs circulating in peripheral blood are enriched for astrocyte-specific glutamine aspartate transporter (GLAST).
“Studies have shown that EVs circulating in the peripheral blood are enriched for L1 cell adhesion molecule (L1CAM), a protein found primarily in the nervous system and is used as a neuronal marker [25, 26] and astrocyte-specific glutamine aspartate transporter (GLAST) [27, 28].”
From Differential RNA packaging into small extracellular vesicles by neurons and astrocytes (2021) · cites this paper as [27]
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“An interesting feature of the exosomes is their capacity to carry various bioactive cargos such as lipids [23], proteins [24,25], miRNAs [26–29], long non-coding RNAs [30,31], etc.”
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Metadata
- Authors
- Goetzl, E. J., Mustapic, M., Kapogiannis, D., Eitan, E., Lobach, I. V., Goetzl, L., Schwartz, J. B., & Miller, B. L.
- Affiliations
- Department of Medicine University of California San Francisco California USA
- Laboratory of Neurosciences National Institutes of Health National Institute on Aging Baltimore Maryland USA
- Clinical Translational Science Institute University of California San Francisco California USA
- Department of Obstetrics, Gynecology Reproductive Sciences Temple University Philadelphia Pennsylvania USA
- Memory and Aging Center Department of Neurology University of California San Francisco California USA
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2016-08-10
- Volume
- 30
- Issue
- 11
- Pages
- 3853-3859
- ISSN
- 0892-6638
- 1530-6860
- Cited by
- 386
- References
- 7
- Language
- en
- Funders
- Michael J. Fox Foundation for Parkinson's Research
- Alzheimer's Association
- Alzheimer’s Research UK
- Weston Brain Institute
- National Institutes of Health (P30 AG028383)
- National Institute on Aging
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