Age-dependent neuronal and synaptic degeneration in mice transgenic for the C terminus of the amyloid precursor protein

Topic: Brain proteins, microglia and lab models

The molecular basis for the degeneration of neurons and the deposition of amyloid in plaques and in the cerebrovasculature in Alzheimer's disease (AD) is incompletely understood. We have proposed that one molecule common to these abnormal processes is a fragment of the Alzheimer amyloid precursor protein (APP) comprising the C-terminal 100 amino acids of this molecule (APP-C100). We tested this hypothesis by creating transgenic mice expressing APP-C100 in the brain.

@article{ostergranite1996-8824314,
  author  = {Oster-Granite, M. L. and McPhie, D. L. and Greenan, J. and Neve, R. L.},
  title   = {{Age-dependent neuronal and synaptic degeneration in mice transgenic for the C terminus of the amyloid precursor protein}},
  journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
  year    = {1996},
  doi     = {10.1523/jneurosci.16-21-06732.1996},
  pmid    = {8824314},
  url     = {https://doi.org/10.1523/jneurosci.16-21-06732.1996}
}

Key findings

• We have proposed that one molecule common to these abnormal processes is a fragment of the Alzheimer amyloid precursor protein (APP) comprising the C-terminal 100 amino acids of this molecule (APP-C100).
• We tested this hypothesis by creating transgenic mice expressing APP-C100 in the brain.
• We report here that aging (18-28 month) APP-C100 transgenic mice exhibit profound degeneration of neurons and synapses in Ammon's horn and the dentate gyrus of the hippocampal formation.
• Of the 106 transgenic mice between 8 and 28 months of age that were examined, all of those older than 18 months displayed severe hippocampal degeneration.

Why it matters

Transgenic mice expressing the C-terminal 100 amino acids of the amyloid precursor protein developed age-dependent degeneration of neurons and synapses in the hippocampus. These are findings in mice about a possible disease mechanism and do not establish any treatment or prevention for humans.

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Study details

• Evidence strengthLow

Read the original

• DOI: 10.1523/jneurosci.16-21-06732.1996
• PubMed: 8824314
• Original source →
• Free full text: Journal of Neuroscience →

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Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment Annals of Neurology · 1991-10-01 · usefulness score 62/100 · Brain tissue and pathology
• Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein Nature · 1995-02-01 · usefulness score 59/100 · 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
• Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation Proceedings of the National Academy of Sciences of the United States of America · 1990-08-01 · usefulness score 48/100 · Risk genes beyond APOE
• The amyloid precursor protein is concentrated in neuronal lysosomes in normal and Alzheimer disease subjects Experimental neurology · 1989-12-01 · usefulness score 46/100 · Risk genes beyond APOE
• Deposition of beta/A4 immunoreactivity and neuronal pathology in transgenic mice expressing the carboxyl-terminal fragment of the Alzheimer amyloid precursor in the brain Proceedings of the National Academy of Sciences of the United States of America · 1992-11-01 · usefulness score 42/100 · Risk genes beyond APOE

Later studies that cite this one

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