Apolipoprotein E decreases tau kinases and phospho-tau levels in primary neurons.

Hoe, Hyang-Sook; Freeman, Jacob; Rebeck, G William

doi:10.1186/1750-1326-1-18

Cited by 45Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Apolipoprotein E decreases tau kinases and phospho-tau levels in primary neurons.

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Hoe, Hyang-Sook, Freeman, Jacob, Rebeck, G William·2006·Molecular Neurodegeneration

DOI 10.1186/1750-1326-1-18PMC PMC1713232

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Abstract

Apolipoprotein E (apoE) receptors act as signaling molecules in neurons, altering phosphorylation of numerous proteins after extracellular ligand binding and affecting neurite outgrowth, synapse formation, and neuronal migration. Since apoE is important in the pathogenesis of Alzheimer's disease (AD), we tested whether apoE treatment of neurons affected molecules important to phosphorylation of tau, such as GSK 3β, P35, and CDK5, and the phosphorylation of tau itself. Treatment of primary neurons with 2 uM apoE (or an apoE-derived peptide) decreased levels of phospho-GSK 3β, P35 and CDK5, and decreased levels of phosphorylated forms of tau. A lower concentration of apoE (100 nM) had no effect on these molecules. The alteration of tau phosphorylation by apoE was blocked by an inhibitor of the low-density lipoprotein receptor family, demonstrating the effects were due to receptor interactions. These results demonstrate that apoE affects several downstream signaling cascades in neurons: decreased tau kinases phosphorylation and inhibition of tau phosphorylation at Thr171 and Ser202/Thr205 epitopes. We conclude that apoE can alter levels of tau kinases and phospho-tau epitopes, potentially affecting tau neuropathological changes seen in AD brains.

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RAP treatment abolished the effect of apoE on tau phosphorylation.
“In addition, RAP treatment abolished the effect of apoE on tau phosphorylation.”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Hoe et al., 2006
The addition of apoE2 caused a strong decrease in phosphorylation of GSK3β and tau, with apoE4 causing the least decrease.
“For example, the addition of apoE2 caused the strong decrease in phosphorylation of GSK 3β and tau, apoE4 the least (Hoe et al., 2006).”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Hoe et al., 2006

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Authors: Hoe, H.-S., Freeman, J., & Rebeck, G. W.
Affiliations: Georgetown University (US)
Corresponding author: Rebeck, G William
ORCID: Hoe, Hyang-Sook
Rebeck, G William
Venue: Molecular Neurodegeneration
Publisher: Springer Science and Business Media LLC
Published: 2006-12
Volume: 1
Issue: 1
Pages: 18-18
ISSN: 1750-1326 (ISSN-L)
DOI: 10.1186/1750-1326-1-18
PMC: PMC1713232
OpenAlex: W2143360246
Cited by: 45
References: 48
Citations by year: 2025: 3 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 2 · 2016: 2 · 2014: 2 · 2013: 1 · 2012: 3
FWCI: 1.77
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Molecular Neurodegeneration (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health (AG14473)
National Institute on Aging (R29AG014473, R01AG014473)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: apolipoprotein E, tau phosphorylation, tau kinases, GSK3β, p35, cyclin-dependent kinase 5, Alzheimer's disease, low-density lipoprotein receptor family, primary neurons, receptor signaling

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Apolipoprotein E decreases tau kinases and phospho-tau levels in primary neurons.

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