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Plaque-type deposition of prion protein in the damaged white matter of sporadic Creutzfeldt-Jakob disease MM1 patients

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Abstract

Plaque-type deposition of prion protein (PrP) in the brain has been extremely rare in sporadic Creutzfeldt-Jakob disease patients with methionine homozygosity at polymorphic codon 129 of the PrP gene and type 1 abnormal isoform of PrP (sCJD-MM1). Here we report three sCJD-MM1 patients who showed prominent PrP-positive amyloid plaques in the cerebral and cerebellar white matter. All three patients showed clinical courses of long duration (2 years ≤), particularly at the end-stage. The white matter of these patients was severely damaged because of the prolonged disease duration. Furthermore, Alzheimer’s amyloid precursor protein, which accumulates within the axonal swellings under pathological conditions, co-accumulated with the PrP-amyloid plaques. These findings suggest that the axonal damage reflecting the prolonged disease duration causes the deposition of PrP-amyloid plaques in the white matter. The present study shows that PrP-amyloid plaques can occur in the white matter of sCJD-MM1 cases.

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Acknowledgments

We thank H. Kudo, K. Abe and M. Kimura for their technical assistance, and B. Bell for critical review of the manuscript. We are grateful to Dr. T. Suzuki for providing the UT-18 antibody. This study was supported by the Program for Promotion of Fundamental Studies in Health Sciences of National Institute of Biomedical Innovation (T.K.), a grant from the Ministry of Health, Labor and Welfare (A.K. and T.K.), and a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (A.K. and T.K.).

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Authors and Affiliations

  1. Division of CJD Science and Technology, Department of Prion Research, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

    Atsushi Kobayashi & Tetsuyuki Kitamoto

  2. Department of Laboratory Medicine, National Center of Neurology and Psychiatry Musashi Hospital, 4-1-1 Ogawa-higashi-machi, Kodaira, 187-8511, Japan

    Kunimasa Arima

  3. Department of Neurology, National Center of Neurology and Psychiatry Musashi Hospital, 4-1-1 Ogawa-higashi-machi, Kodaira, 187-8511, Japan

    Masafumi Ogawa & Miho Murata

  4. Division of Neuropathology, Department of Neuroscience, Research Center for Medical Sciences, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, 105-8461, Japan

    Takahiro Fukuda

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  1. Atsushi Kobayashi
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  2. Kunimasa Arima
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  3. Masafumi Ogawa
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  4. Miho Murata
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  5. Takahiro Fukuda
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  6. Tetsuyuki Kitamoto
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Correspondence to Tetsuyuki Kitamoto.

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Kobayashi, A., Arima, K., Ogawa, M. et al. Plaque-type deposition of prion protein in the damaged white matter of sporadic Creutzfeldt-Jakob disease MM1 patients. Acta Neuropathol 116, 561–566 (2008). https://doi.org/10.1007/s00401-008-0425-8

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  • DOI: https://doi.org/10.1007/s00401-008-0425-8

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