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Markers of apoptosis and models of programmed cell death in Alzheimer’s disease

  • Jacques Hugon
  • F. Terro
  • F. Esclaire
  • C. Yardin
Conference paper

Abstract

Alzheimer’s disease (AD) is neuropathologically marked by the presence of senile plaques composed of β-amyloid peptide and by neurofibrillary tangles formed by abnormally phosphorylated tau protein. Many authors have also reported a neuronal loss in affected regions of the brain in AD patients. This neuronal degeneration could be linked to the triggering of intracellular pathways leading to apoptosis. Previous works were focused on the links between neuronal apoptosis and tau and amyloid precursor protein (APP) metabolisms. We have analyzed tau gene expression in primary neuronal cultures submitted to an apoptotic stress produced by excitotoxicity or serum deprivation. Glutamate induces an enhancement of tau gene expression in resistant neurons whereas a reduced expression is noted in apoptotic cells. This decrease is similar to what is observed after trophic support withdrawal in neuronal cultures. Neurons expressing phosphorylated tau are more resistant to experimental apoptosis than neurons positively labeled for de- phosphorylated tau protein (AT8/Tau 1 epitope). In vitro apoptotic neurons are able to produce membrane blebbings (strongly immunopositive for APP and amyloidogenic fragments) that are secondary released in the extracellular space. Finally neurons overexpressing human mutated presenilin 1 (M146 L) are more prone to degenerate than neurons overexpressing human wild-type presenilin 1 after apoptosis induction. Alzheimer’s disease (AD) is neuropathologically marked by the presence of senile plaques containing an accumulation of the β-amyloid peptide, by neurofibrillary tangles made of intraneuronal hyperphosphorylated tau protein and also by neuronal loss observed by a majority of authors. The cause of neuronal death in AD is unknown although a growing body of evidence suggests that the accumulation of extracellular (and/or intracellular) (3- amyloid peptide could trigger a toxic neuronal degeneration. Trying to find out the origin of neuronal loss in AD is a crucial point since this could lead to the introduction of neuroprotective strategies in future treatments of this disease. Of course this prospective could also be applied to all neurodegenerative diseases. Recent findings suggest that apoptosis could play a role in cell loss detected in AD although this issue is still debated among physicians and medical scientists. This short review will focus on apoptosis and cellular and transgenic model of AD.

Keywords

Amyotrophic Lateral Sclerosis Amyloid Precursor Protein Neuronal Apoptosis Senile Plaque Serum Deprivation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Jacques Hugon
    • 2
  • F. Terro
    • 1
  • F. Esclaire
    • 1
  • C. Yardin
    • 1
  1. 1.Department of Histology and Cell Biology, Faculty of MedicineUniversity of LimogesLimogesFrance
  2. 2.Department of Anatomy, Faculty of MedicineUniversity of Hong KongHong KongChina

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