Vascular variant of prion protein cerebral amyloidosis with τ-positive neurofibrillary tangles: The phenotype of the stop codon 145 mutation in PRNP

Bernardino Ghetti, Pedro Piccardo, Maria Grazia Spillantini, Yousuke Ichimiya, Monica Porro, Francesco Perini, Tetsuyuki Kitamoto, Jun Tateishi, Charles Seiler, Blas Frangione, Orso Bugiani, Giorgio Giaccone, Frances Prelli, Michel Goedert, Stephen R. Dlouhy, Fabrizio Tagliavini

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Abstract

Deposition of PrP amyloid in cerebral vessels in conjunction with neurofibrillary lesions is the neuropathologic hallmark of the dementia associated with a stop mutation at codon 145 of PRNP, the gene encoding the prion protein (PrP). In this disorder, the vascular amyloid in tissue sections and the ≃7.5-kDa fragment extracted from amyloid are labeled by antibodies to epitopes located in the PrP sequence including amino acids 90- 147. Amyloid-laden vessels are also labeled by antibodies against the C terminus, suggesting that PrP from the normal allele is involved in the pathologic process. Abundant neurofibrillary lesions are present in the cerebral gray matter. They are composed of paired helical filaments, are labeled with antibodies that recognize multiple phosphorylation sites in τ protein, and are similar to those observed in Alzheimer disease. A PrP cerebral amyloid angiopathy has not been reported in diseases caused by PRNP mutations or in human transmissible spongiform encephalopathies; we propose to name this phenotype PrP cerebral amyloid angiopathy (PrP-CAA).

Original languageEnglish (US)
Pages (from-to)744-748
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number2
DOIs
StatePublished - Jan 23 1996

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Ghetti, B., Piccardo, P., Spillantini, M. G., Ichimiya, Y., Porro, M., Perini, F., Kitamoto, T., Tateishi, J., Seiler, C., Frangione, B., Bugiani, O., Giaccone, G., Prelli, F., Goedert, M., Dlouhy, S. R., & Tagliavini, F. (1996). Vascular variant of prion protein cerebral amyloidosis with τ-positive neurofibrillary tangles: The phenotype of the stop codon 145 mutation in PRNP. Proceedings of the National Academy of Sciences of the United States of America, 93(2), 744-748. https://doi.org/10.1073/pnas.93.2.744