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

Topic: Brain proteins, microglia and lab models

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.

Key findings

• 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.

Why it matters

This study found that human neurons derived from a teratocarcinoma cell line express only the 695-amino acid APP isoform and produce intracellular amyloid-beta peptides. It is laboratory cell research and does not test any treatment, cure, or prevention.

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Study details

• Evidence strengthLow

Read the original

• DOI: 10.1073/pnas.90.20.9513
• PubMed: 8415732
• Original source →
• Free full text: PubMed Central →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{wertkin1993-8415732,
  author  = {Wertkin, A. M. and Turner, R. S. and Pleasure, S. J. and Golde, T. E. and Younkin, S. G. and Trojanowski, J. Q. and Lee, V. M.},
  title   = {{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}},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year    = {1993},
  doi     = {10.1073/pnas.90.20.9513},
  pmid    = {8415732},
  url     = {https://doi.org/10.1073/pnas.90.20.9513}
}

Studies this one cites

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• The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor Nature · 1987-02-01 · usefulness score 58/100 · Disease mechanisms
• Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport Proceedings of the National Academy of Sciences of the United States of America · 1990-02-01 · usefulness score 50/100 · Risk genes beyond APOE
• Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues Proceedings of the National Academy of Sciences of the United States of America · 1988-10-01 · usefulness score 49/100 · Risk genes beyond APOE
• Increased expression of beta-amyloid precursor protein during neuronal differentiation is not accompanied by secretory cleavage Proceedings of the National Academy of Sciences of the United States of America · 1992-10-01 · usefulness score 45/100 · Risk genes beyond APOE

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