NR AWFI
AU Ghetti,B.
TI Gerstmann-Sträussler-Scheinker Disease (GSS) and prion protein cerebral amyloid angiopathy (PrP-CAA)
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Oral sessions ORAL-26
PT Konferenz-Vortrag
AB GSS and PrP-CAA are degenerative dementias inherited in an autosomal dominant pattern and associated with the deposition of PrP in the cerebral parenchyma and cerebral blood vessels, respectively. GSS has been found to be associated with ten missense mutations in PRNP. PrP-CAA has been found to be associated with three nonsense mutations in PRNP. We report clinical, and genetic data collected from 34 affected and 19 unaffected gene-carriers from 7 families in which the following mutations in the PRNP gene were found: P102L-129M, A117V-129V, H187R-129V, F198S129V. We report pathologic, and genetic data collected from 52 affected and 3 unaffected gene-carriers from 15 families in which the following mutations in the PRNP gene were found: P102L129M, P102L-129V, A117V-129V, G131V-129M, Y145STOP-129M, H187R-129V, F198S-129V, D202N-129V, Q212P-129M, Q217R-129V. Clinically, GSS is characterized by a movement disorder and dementia. PrP-CAA is characterized by a dementing illness reminiscent of Alzheimer disease. The age at onset varies between the fourth and eighth decades; however, in GSS associated with the F198S mutation, we have observed a statistically significant difference (p<0.001) in the mean age at onset of clinical signs between individuals homozygous for valine at residue 129 (mean: 43.7 years) and individuals heterozygous methionine/valine at residue 129 (mean: 56.5 years). Pathologically, deposition of intraneuronal insoluble tau occurs in association with the Y145STOP, F198S, D202N and Q217R mutations while it is sporadically present in association with the A117V and H187R. Spongiform degeneration is only seen in GSS associated with the P102L mutation, but not in all cases. Transmission of GSS into experimental animals has been shown to occur only following the inoculation of brain tissue from individuals with the P102L mutation.
AD Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA
SP englisch
PO Italien