Jan 14, 2016

Alzheimer's disease-like APP processing in wild-type mice identifies synaptic defects as initial steps of disease progression

Molecular Neurodegeneration
Mickael AudrainJérôme Braudeau

Abstract

Alzheimer's disease (AD) is the most frequent form of dementia in the elderly and no effective treatment is currently available. The mechanisms triggering AD onset and progression are still imperfectly dissected. We aimed at deciphering the modifications occurring in vivo during the very early stages of AD, before the development of amyloid deposits, neurofibrillary tangles, neuronal death and inflammation. Most current AD models based on Amyloid Precursor Protein (APP) overproduction beginning from in utero, to rapidly reproduce the histological and behavioral features of the disease within a few months, are not appropriate to study the early steps of AD development. As a means to mimic in vivo amyloid APP processing closer to the human situation in AD, we used an adeno-associated virus (AAV)-based transfer of human mutant APP and Presenilin 1 (PS1) genes to the hippocampi of two-month-old C57Bl/6 J mice to express human APP, without significant overexpression and to specifically induce its amyloid processing. The human APP, βCTF and Aβ42/40 ratio were similar to those in hippocampal tissues from AD patients. Three months after injection the murine Tau protein was hyperphosphorylated and rapid synaptic failure occurred charact...Continue Reading

  • References58
  • Citations8

References

  • References58
  • Citations8

Citations

Mentioned in this Paper

Arsa
DLG4
Familial Alzheimer Disease (FAD)
In Vivo
Biochemical Pathway
GRIN1
Laboratory Procedures
APP protein, human
Genes
Neurofibrillary Degeneration (Morphologic Abnormality)

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