Co-expression of β-amyloid precursor protein (βAPP) and apolipoprotein E in cell culture: analysis of βAPP processing
Open accessAbstract
Apolipoprotein E (ApoE) is the major genetic risk factor for Alzheimer's disease (AD). The ApoE4 allele is associated with earlier disease onset and greater cerebral deposition of the amyloid beta peptide (Abeta), the major constituent of senile (amyloid) plaques. The molecular mechanism underlying these effects of ApoE4 remains unclear; ApoE alleles could have different influences on Abeta production, extracellular aggregation, or clearance. Because the missense mutations on chromosomes 14 and 21 that cause familial forms of AD appear to lead to increased secretion of Abeta, it is important to determine whether ApoE4 has a similar effect. Here, we have examined the effects of all three ApoE alleles on the processing of betaAPP and the secretion of Abeta in intact cells. We established neural (HS683 human glioma) and non-neural (Chinese hamster ovary) cell culture systems that constitutively secrete both ApoE and Abeta at concentrations like those in human cerebrospinal fluid. betaAPP metabolites, generated in the presence of each ApoE allele, were analysed and quantified by two methods: immunoprecipitation and phosphorimaging, and ELISA. We detected no consistent allele-specific effects of ApoE on betaAPP processing in either cell type. Our data suggest that the higher amyloid burden found in AD subjects expressing ApoE4 is not due to increased amyloidogenic processing of betaAPP, in contrast to findings in AD linked to chromosome 14 or 21. These co-expressing cell lines wil…
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A previous in vitro study showed no effect of apoE isoforms on APP processing.
“Overall, our results in PDAPP/TRE mice are consistent with a previous in vitro study showing no effect of apoE isoforms on APP processing (42).”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [42]
Others found no clear evidence for isoform-specific effects on APP processing.
“However, others found no clear evidence for isoform-specific effects on APP processing (Biere et al., 1995; Cedazo-Minguez et al., 2001; Irizarry et al., 2004).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Biere et al., 1995
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- Authors
- Biere, A. L., Ostaszewski, B., Zhao, H., Gillespie, S., Younkin, S. G., & Selkoe, D. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Case Western Reserve University (US)
- Corresponding author
- Selkoe, Dennis J.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 1995-06
- Volume
- 2
- Issue
- 3
- Pages
- 177-187
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2064901225
- Cited by
- 52
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 1 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Institute on Aging (AG 12749, AG-06173, R01AG012749)
- 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, APOE ε4, amyloid precursor protein, amyloid-beta secretion, Alzheimer's disease, amyloid-beta, amyloidogenic processing, APOE alleles, familial Alzheimer's disease, amyloid plaques, glioma cells, CHO cells
- MeSH terms
- Alzheimer Disease, Animals, Apolipoproteins E, Base Sequence, Brain, Brain Chemistry, Cells, Cultured, Chromosomes, Human, Pair 14, Cloning, Molecular, Enzyme-Linked Immunosorbent Assay, Cricetinae, Humans, Molecular Sequence Data, Precipitin Tests, Blotting, Western, Amyloid beta-Protein Precursor, Point Mutation, Cell Culture Techniques
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