Staff member


Lucía Gutiérrez Chamorro

Laboratory Assistant
Nanomalaria
lgutierrez@ibecbarcelona.eu
+34 932 275 400
Staff member publications

Alzheimer's disease (AD) is characterized by the presence of amyloid plaques mainly consisting of hydrophobic β-amyloid peptide (Aβ) aggregates and neurofibrillary tangles (NFTs) composed principally of hyperphosphorylated tau. Aβ oligomers have been described as the earliest effectors to negatively affect synaptic structure and plasticity in the affected brains, and cellular prion protein (PrPC) has been proposed as receptor for these oligomers. The most widely accepted theory holds that the toxic effects of Aβ are upstream of change in tau, a neuronal microtubule-associated protein that promotes the polymerization and stabilization of microtubules. However, tau is considered decisive for the progression of neurodegeneration, and, indeed, tau pathology correlates well with clinical symptoms such as dementia. Different pathways can lead to abnormal phosphorylation, and, as a consequence, tau aggregates into paired helical filaments (PHF) and later on into NFTs. Reported data suggest a regulatory tendency of PrPC expression in the development of AD, and a putative relationship between PrPC and tau processing is emerging. However, the role of tau/PrPC interaction in AD is poorly understood. In this study, we show increased susceptibility to Aβ-derived diffusible ligands (ADDLs) in neuronal primary cultures from PrPC knockout mice, compared to wild-type, which correlates with increased tau expression. Moreover, we found increased PrPC expression that paralleled with tau at early ages in an AD murine model and in early Braak stages of AD in affected individuals. Taken together, these results suggest a protective role for PrPC in AD by downregulating tau expression, and they point to this protein as being crucial in the molecular events that lead to neurodegeneration in AD.

Keywords: Aβ oligomers, Alzheimer's disease, Cellular prion protein, Microtubule-associated protein tau


Alzheimer's disease and prion diseases are neuropathological disorders that are caused by abnormal processing and aggregation of amyloid and prion proteins. Interactions between amyloid precursor protein (APP) and PrPc proteins have been described at the neuron level. Accordingly to this putative interaction, we investigated whether β-amyloid accumulation may affect prion infectivity and, conversely, whether different amounts of PrP may affect β-amyloid accumulation. For this purpose, we used the APPswe/PS1dE9 mouse line, a common model of Alzheimer's disease, crossed with mice that either overexpress (Tga20) or that lack prion protein (knock-out) to generate mice that express varying amounts of prion protein and deposit β-amyloid. On these mouse lines, we investigated the influence of each protein on the evolution of both diseases. Our results indicated that although the presence of APP/PS1 and β-amyloid accumulation had no effect on prion infectivity, the accumulation of β-amyloid deposits was dependent on PrPc, whereby increasing levels of prion protein were accompanied by a significant increase in β-amyloid aggregation associated with aging.

Keywords: Aging, Amyloid, Neurodegeneration, Prion, Signaling


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