Joaquín Castilla
in CIC bioGUNE

Researchers from the Center for Cooperative Research, CIC bioGUNE, and the University of Texas Medical School, Houston (USA), have discovered a new relation between Alzheimer's and prion diseases. The fundamentals for this conclusion are based on the misfolding of prion proteins involved in such diseases. The work has been published in the April issue of the Journal of Neuroscience.

The project, lead by researchers Joaquin Castilla (CIC bioGUNE) and Claudio Solo (University of Texas Medical School), assumes that, despite the diversity of clinical symptoms associated with misfolded protein diseases, there is a great resemblance suggesting that many of these diseases might share an important relation on a mechanical-molecular level.

The main goal of this study was to analyse the interaction between the misfolded proteins involved in Alzheimer's and prion diseases. The latter belong to a group of neurodegenerative diseases that affect humans and animals alike and for which there is no available treatment, like scrapie or BSE (Bovine Spongiform Encephalopathy). In order to study this connection, prions were inoculated in a model Alzheimer's disease transgenic mouse developing amyloid plaques.

"Our findings show a dramatic acceleration and exacerbation of both pathologies. In particular, the clinical signs of prion disease symptoms in transgenic mice appeared significantly faster with a concomitant increase on the level of misfolded prion protein in the brain. Likewise, a striking increase in amyloid plaque deposition was observed, characteristic of Alzheimer's disease", states Joaquin Castilla, Head of the Prion Lab of the Proteomics Unit at CIC bioGUNE.

The histological and biochemical study showed the physical relationship between both misfolded proteins in the brain and the in vitro experiments proved that protein misfolding may be favoured in vitro in a heterologous form (i.e., the prion protein favours misfolding of the protein giving rise to Alzheimer's plaques).

In conclusion, this suggests a close and deep interaction between Alzheimer's and prion diseases, implying that protein misfolding may be a significant risk factor in the development of a second disease. "This study may have important implications in understanding the origin and progress of diseases that involve protein misfolding", concludes Castilla.

The techniques used are common to both pathologies, prion diseases and Alzheimer's. These include inoculation of model animals, as well as histological-pathological and immunohistochemistry studies, biochemical techniques and in vitro protein replication studies.