Viorica Chelban, Andreea Manole, Lasse Pihlstrøm, Lucia Schottlaender, Stephanie Efthymiou, Emer OConnor, Wassilios Meissner, Janice L. Holton, Henry Houlden
Neurobiology of Aging,
Neurodegenerative diseases are a very diverse group of disorders but they share some common mechanisms such as abnormally misfolded proteins with prion-like propagation and aggregation. Creutzfeldt - Jakob disease (CJD) is the most prevalent prion disease in humans. In the sporadic form of CJD the only known risk factor is the codon 129 polymorphism. Recent reports suggested that α-synuclein in MSA has similar pathogenic mechanisms as the prion protein (PrP). Here we present one Italian family with MSA and prion disease. Also, cases of concurrent MSA and prion pathology in the same individual or family suggest the possibility of molecular interaction between PrP and α-synuclein in the process of protein accumulation and neurodegeneration, warranting further investigations.
We assessed the PRNP gene by whole exome sequencing in 264 pathologically confirmed MSA cases and 462 healthy controls to determine whether the two diseases share similar risk factors. We then analyzed codon 129 polymorphism by Sanger sequencing and compared with previously published results in sCJD. Homozygosity at codon 129 was present in 50% of pathologically confirmed MSA cases and in 58% of normal controls (OR 0.7 (95% CI of 0.5-0.9) compared with 88.2% in sCJD. Our data shows that the homozygous state of position 129 in the PRNP is not a risk factor for MSA. No other variants in the PRNP gene were associated with increased risk for MSA.