Prion protein and Abeta-related synaptic toxicity impairment.
Alzheimer's disease (AD), the most common neurodegenerative disorder, goes along with extracellular amyloid-beta (Abeta) deposits. The cognitive decline observed during AD progression correlates with damaged spines, dendrites and synapses in hippocampus and cortex. Numerous studies have shown that Abeta oligomers, both synthetic and derived from cultures and AD brains, potently impair synaptic structure and functions. The cellular prion protein (PrP(C)) was proposed to mediate this effect. We report that ablation or overexpression of PrP(C) had no effect on the impairment of hippocampal synaptic plasticity in a transgenic model of AD. These findings challenge the role of PrP(C) as a mediator of Abeta toxicity.
Calella
Anna Maria
AM
Institute of Neuropathology, University Hospital Zürich, Zürich, Switzerland.
Farinelli
Mélissa
M
Nuvolone
Mario
M
Mirante
Osvaldo
O
Moos
Rita
R
Falsig
Jeppe
J
Mansuy
Isabelle M
IM
Aguzzi
Adriano
A
D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000473:pathology*
D016229:Amyloid beta-Peptides; D011328:Prions