Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system.
Open accessAbstract
The plasma protein apolipoprotein (apo) E is an important determinant of lipid transport and metabolism in mammals. In the present study, immunocytochemistry has been used to identify apo E in specific cells of the central and peripheral nervous systems of the rat. Light microscopic examination revealed that all astrocytes, including specialized astrocytic cells (Bergmann glia of the cerebellum, tanycytes of the third ventricle, pituicytes of the neurohypophysis, and Müller cells of the retina), possessed significant concentrations of apo E. In all of the major subdivisions of the central nervous system, the perinuclear region of astrocytic cells, as well as their cell processes that end on basement membranes at either the pial surface or along blood vessels, were found to be rich in apo E. Extracellular apo E was present along many of these same surfaces. The impression that apo E is secreted by astrocytic cells was confirmed by electron microscopic immunocytochemical studies, which demonstrated the presence of apo E in the Golgi apparatus. Apo E was not present in neurons, oligodendroglia, microglia, ependymal cells, and choroidal cells. In the peripheral nervous system, apo E was present within the glia surrounding sensory and motor neurons; satellite cells of the dorsal root ganglia and superior cervical sympathetic ganglion as well as the enteric glia of the intestinal ganglia were reactive. Apo E was also present within the non-myelinating Schwann cells but not within the myelinating Schwann cells of peripheral nerves. These results suggest that apo E has an important, previously unsuspected role in the physiology of nervous tissue.
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In a normal brain, apoE is produced predominantly by astrocytes, and to a much less extent by microglia.
“In a normal brain, apoE is produced predominantly by astrocytes, and to a much less extent, by microglia (Boyles et al., 1985; Uchihara et al., 1995).”
From Overexpressing low‐density lipoprotein receptor reduces tau‐associated neurodegeneration in relation to apoE‐linked mechanisms (2021) · cites this paper as Boyles et al., 1985
The Abstract reports apoE in astrocytes of rat brain but says it was not present in microglia. The Discussion likewise says most cells identified as microglia were negative for apoE immunoreactivity. The source therefore supports astrocytic production, but not the claim that normal-brain microglia produce apoE to a lesser extent. (LLM, conf=0.87)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredCholesterol, HDL-like particles, and apolipoprotein E are synthesized in situ by glial cells.
“Therefore, cholesterol, HDL-like particles, and apolipoprotein E (ApoE) are synthesized in situ by glial cells [16–18].”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [16]
The Discussion (page not available) identifies apoE as a secretory product of astrocytes and reports that cultured astrocytes produce it. The paper does not establish that glial cells synthesize cholesterol or HDL-like particles in situ; it discusses cholesterol transport and HDL particles, not their synthesis by glia. (LLM, conf=0.88)
Experimental — accuracy not yet measuredApolipoprotein E is expressed in the central and peripheral nervous systems.
“Apolipoprotein E is expressed in the central and peripheral nervous systems.38”
From Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function (2014) · cites this paper as [38]
APOE is not transferred over the blood brain barrier, suggesting astrocytes are the main contributor of APOE in the brain.
“However, APOE is not transferred over the blood brain barrier (Huynh et al, 2019; Lane-Donovan et al, 2016) suggesting that astrocytes are the main contributor of APOE in the brain (Boyles et al, 1985; Zhang et al, 2014).”
From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Boyles et al, 1985
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Henningfield, C. M., Arreola, M. A., Soni, N., Spangenberg, E. E., & Green, K. N. (2022) · Glia · doi:10.1002/glia.24105 · Cited by 40 · see citing works
Characterization of a new apolipoprotein E5 variant detected in two French-Canadian subjects
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Opposing Roles of apolipoprotein E in aging and neurodegeneration
Hudry, E., Klickstein, J., Cannavo, C., Jackson, R., Muzikansky, A., Gandhi, S., Urick, D., Sargent, T., Wrobleski, L., Roe, A. D., et al. (2019) · Life Science Alliance · doi:10.26508/lsa.201900325 · Cited by 30 · see citing works
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High-density lipoprotein-related cholesterol metabolism in Alzheimer's disease
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Protective ApoE variants support neuronal function by effluxing oxidized phospholipids
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Current insights into apolipoprotein E and the immune response in Alzheimer's disease
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Protective ApoE variants support neuronal function by extracting peroxidated lipids
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ApoE expression across the CNS: Who, What, Where, When, and How (much)?
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- Authors
- Boyles, J. K., Pitas, R. E., Wilson, E., Mahley, R. W., & Taylor, J. M.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1985-10-01
- Volume
- 76
- Issue
- 4
- Pages
- 1501-1513
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC424114
- OpenAlex
- W2147413218
- Cited by
- 829
- References
- 1
- Citations by year
- 2026: 22 · 2025: 26 · 2024: 17 · 2023: 29 · 2022: 22 · 2021: 23 · 2020: 22 · 2019: 22 · 2018: 8 · 2017: 21 · 2016: 17 · 2015: 15 · 2014: 17 · 2013: 18 · 2012: 17
- FWCI
- 12.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- apolipoprotein E, astrocytes, Bergmann glia, tanycytes, pituicytes, Müller cells, satellite cells, dorsal root ganglia, superior cervical ganglion, enteric glial cells, Golgi apparatus, lipid transport, central nervous system, peripheral nervous system
- MeSH terms
- Animals, Apolipoproteins A, Apolipoproteins E, Astrocytes, Brain Chemistry, Female, Kidney, Liver, Male, Muscles, Neuroglia, Peripheral Nerves, Rats, Inbred Strains, Retina, Apolipoprotein A-I, Mice, Rats
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