Cited by 231Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Human neurons derived from a teratocarcinoma cell line express solely the 695-amino acid amyloid precursor protein and produce intracellular beta-amyloid or A4 peptides.

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Wertkin, A M, Turner, R S, Pleasure, S J, Golde, T E, Younkin, S G, Trojanowski, J Q, Lee, V M·1993·Proceedings of the National Academy of Sciences

Abstract

The beta-amyloid or beta/A4 peptides that accumulate as filamentous aggregates in the extracellular space of Alzheimer disease (AD) brains are derived from one or more alternatively spliced amyloid precursor proteins (APPs). The more abundant APPs in the central nervous system are the 695-(APP695), 751- (APP751), and 770- (APP770) amino acid isoforms, and each could be the source of beta/A4 peptide that accumulates in the AD brain. It is plausible that altered metabolism of these APPs by central nervous system neurons could lead to the release and deposition of beta/A4 peptide in brain parenchyma. Thus, we examined the expression and processing of the three major brain APPs in nearly pure human neurons (NT2N cells) derived from a teratocarcinoma cell line (NTera2/c1.D1 or NT2 cells) after retinoic acid treatment. NT2N neurons expressed almost exclusively APP695, whereas NT2 cells expressed predominantly APP751/770. Furthermore, the processing of the APPs in NT2N cells was distinct from NT2 and nonneuronal cells. Most significantly, the NT2N neurons but not the NT2 cells constitutively generated intracellular beta/A4 peptide and released it into the culture medium. This work demonstrates the intracellular production of beta/A4 peptide and suggests that cultured NT2N cells may provide a unique model system for understanding the contribution of neurons and APP695 to amyloidogenesis in the AD brain.

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Crossref · 10.1073/pnas.90.20.9513

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Authors
Wertkin, A. M., Turner, R. S., Pleasure, S. J., Golde, T. E., Younkin, S. G., Trojanowski, J. Q., & Lee, V. M.
Affiliations
University of Pennsylvania (US)
Venue
Proceedings of the National Academy of Sciences
Published
1993-10-15
Volume
90
Issue
20
Pages
9513-9517
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2061798362
Cited by
231
References
34
Citations by year
2026: 3 · 2025: 6 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 2 · 2020: 7 · 2019: 2 · 2018: 8 · 2017: 6 · 2015: 3 · 2014: 6 · 2013: 5 · 2012: 12
FWCI
10.22
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (AG-09215)
  • National Institute on Aging (AG09215, AG06656, P01AG009215, R01AG006656)
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
amyloid precursor protein, APP695, APP751, APP770, amyloid-beta, Alzheimer's disease, amyloidogenesis, neuronal differentiation, retinoic acid, APP processing, cultured neurons
MeSH terms
Cell Differentiation, Glycosylation, Humans, Neurons, Protein Processing, Post-Translational, RNA, Messenger, Tretinoin, Tumor Cells, Cultured, Gene Expression, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Teratocarcinoma

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