Chronic elevation of S100 beta protein does not alter APP mRNA expression or promote beta-amyloid deposition in the brains of aging transgenic mice

Topic: Brain proteins, microglia and lab models

S100 beta protein, a member of a Ca(2+)-binding protein family present primarily in the nervous system, affects the survival and differentiation of both neurons and glia cells. Elevated levels of S100 beta protein have been observed in the brains of individuals with Alzheimer Disease (AD), as well as in those with Down Syndrome (DS). We have examined transcript levels from the gene encoding the amyloid precursor protein (APP) in four brain regions of mice from 1 to 24 months of age. After stable adult levels of expression are reached, APP mRNA levels do not change with aging. APP mRNA levels are independent of normal regional variation in S100 beta mRNA and protein. Further, chronic exposure to S100 beta elevated 2- or 7-fold above normal did not alter the transcript levels of APP in transgenic mice. These results leave open the possibility of focal changes in APP transcription and do not address possible effects of S100 beta on the complex processing known to occur with APP protein. However, neither control nor transgenic aged mice showed any evidence of abnormal deposition of amyloid in neuritic plaques. These results are discussed in the context of hypotheses about the role of elevated S100 beta in DS and AD.

Key findings

• These results leave open the possibility of focal changes in APP transcription and do not address possible effects of S100 beta on the complex processing known to occur with APP protein.
• These results are discussed in the context of hypotheses about the role of elevated S100 beta in DS and AD.

Why it matters

In this mouse study, raising S100 beta protein two- or seven-fold above normal did not change APP mRNA levels, and neither control nor transgenic aged mice showed abnormal amyloid deposits in plaques. The authors note this does not rule out focal changes in APP transcription or effects on APP protein processing, so it leaves the role of S100 beta in Alzheimer's disease unresolved.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/0006-8993(95)00991-7
• PubMed: 8846093
• Original source →
• Free full text: Brain Research →

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

@article{yao1995-8846093,
  author  = {Yao, J. and Kitt, C. and Reeves, R. H.},
  title   = {{Chronic elevation of S100 beta protein does not alter APP mRNA expression or promote beta-amyloid deposition in the brains of aging transgenic mice}},
  journal = {Brain research},
  year    = {1995},
  doi     = {10.1016/0006-8993(95)00991-7},
  pmid    = {8846093},
  url     = {https://doi.org/10.1016/0006-8993(95)00991-7}
}

Studies this one cites

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• Alzheimer's disease in Down's syndrome: clinicopathologic studies Neurology · 1985-07-01 · usefulness score 61/100 · Getting a diagnosis
• Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein Nature · 1995-02-01 · usefulness score 59/100 · Risk genes beyond APOE
• Astrocytosis and axonal proliferation in the hippocampus of S100b transgenic mice Proceedings of the National Academy of Sciences of the United States of America · 1994-06-01 · usefulness score 41/100 · Down syndrome and Alzheimer's

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