Extraneural Pathologic Prion Protein
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《新英格兰医药杂志》
To the Editor: Glatzel et al. (Nov. 6 issue)1 report extraneural localization of pathologic prion protein (PrPSc) in patients with sporadic Creutzfeldt–Jakob disease. They report that PrPSc could be identified in spleen and muscle specimens from approximately one third of patients with this disease. It would be interesting to search for PrPSc in the peripheral nervous system in these patients, particularly those with PrPSc in skeletal muscle. A previous immunohistochemical study showed the accumulation of prion protein in the dorsal roots of a patient with sporadic Creutzfeldt–Jakob disease.2 Using immunohistochemistry and Western blot analyses in seven cases of sporadic Creutzfeldt–Jakob disease, we found disease-associated overexpression of normal cellular prion protein (PrPC) in the peripheral nerves of a valine-homozygous patient with type 1 sporadic Creutzfeldt–Jakob disease.3 Moreover, we identified PrPSc in the dorsal-root ganglia and the superficial peroneal nerve in a methionine-homozygous patient with type 1 sporadic Creutzfeldt–Jakob disease.4,5 We agree with Glatzel et al. that such studies need to be performed in a larger cohort with the use of more sensitive Western blot methods.
Alexandre Favereaux, Ph.D.
Victor Segalen–Bordeaux 2 University
33076 Bordeaux, France
Armand Perret-Liaudet, Ph.D.
Neurology and Neurosurgery Hospital
69394 Lyons, France
Anne Vital, M.D., Ph.D.
Victor Segalen–Bordeaux 2 University
33076 Bordeaux, France
anne.vital@neuropath.u-bordeaux2.fr
References
Glatzel M, Abela E, Maissen M, Aguzzi A. Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N Engl J Med 2003;349:1812-1820.
Hainfellner JA, Budka H. Disease associated prion protein may deposit in the peripheral nervous system in human transmissible spongiform encephalopathies. Acta Neuropathol (Berl) 1999;98:458-460.
Favereaux A, Quadrio I, Perret-Liaudet A, et al. Prion protein accumulation involving the peripheral nervous system in a sporadic case of Creutzfeldt-Jakob disease. Neuropathol Appl Neurobiol 2003;29:602-605.
Vital A, Favereaux A, Perret-Liaudet A, et al. Prion protein accumulation involving the peripheral nervous system in some sporadic cases of Creutzfeldt-Jakob disease. Brain Pathol 2003;13:Suppl:S150-S150. abstract.
Favereaux A, Quadrio I, Vital C, et al. Pathologic prion protein spreading in the peripheral nervous system of a patient with sporadic Creutzfeldt-Jakob disease. Arch Neurol (in press).
The authors reply: We detected PrPSc in muscle specimens from one fourth of patients who had died with sporadic Creutzfeldt–Jakob disease. This result may be due to limitations of the assay or may point to differences in pathogenesis between patients with PrPSc-positive and PrpSc-negative muscle specimens. Favereaux et al. raise the intriguing question of whether the presence of PrPSc in skeletal muscle might correlate with the way in which prions affect the sensory peripheral nervous system. Murine prions can invade not only sensory tracts but also arms of the sympathetic peripheral nervous system,1 and the location of immune cells in relation to sympathetic nerves appears to control the efficacy of prion neuroinvasion.2 Should the above correlations apply to sporadic Creutzfeldt–Jakob disease in humans, it would be important to identify by what means (and in which direction) prions move between the peripheral nervous system and muscle. These questions could be addressed by studying prion inoculation of suitable transgenic animal models, such as those exhibiting PrP expression restricted to the peripheral nervous system or muscle.3
Adriano Aguzzi, M.D., Ph.D.
Markus Glatzel, M.D.
Institute of Neuropathology
CH-8091 Zurich, Switzerland
adriano@pathol.unizh.ch
References
Glatzel M, Heppner FL, Albers KM, Aguzzi A. Sympathetic innervation of lymphoreticular organs is rate limiting for prion neuroinvasion. Neuron 2001;31:25-34.
Prinz M, Heikenwalder M, Junt T, et al. Positioning of follicular dendritic cells within the spleen controls prion neuroinvasion. Nature 2003;425:957-962.
Glatzel M, Flechsig E, Navarro B, et al. Adenoviral and adeno-associated viral transfer of genes to the peripheral nervous system. Proc Natl Acad Sci U S A 2000;97:442-447.
Alexandre Favereaux, Ph.D.
Victor Segalen–Bordeaux 2 University
33076 Bordeaux, France
Armand Perret-Liaudet, Ph.D.
Neurology and Neurosurgery Hospital
69394 Lyons, France
Anne Vital, M.D., Ph.D.
Victor Segalen–Bordeaux 2 University
33076 Bordeaux, France
anne.vital@neuropath.u-bordeaux2.fr
References
Glatzel M, Abela E, Maissen M, Aguzzi A. Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N Engl J Med 2003;349:1812-1820.
Hainfellner JA, Budka H. Disease associated prion protein may deposit in the peripheral nervous system in human transmissible spongiform encephalopathies. Acta Neuropathol (Berl) 1999;98:458-460.
Favereaux A, Quadrio I, Perret-Liaudet A, et al. Prion protein accumulation involving the peripheral nervous system in a sporadic case of Creutzfeldt-Jakob disease. Neuropathol Appl Neurobiol 2003;29:602-605.
Vital A, Favereaux A, Perret-Liaudet A, et al. Prion protein accumulation involving the peripheral nervous system in some sporadic cases of Creutzfeldt-Jakob disease. Brain Pathol 2003;13:Suppl:S150-S150. abstract.
Favereaux A, Quadrio I, Vital C, et al. Pathologic prion protein spreading in the peripheral nervous system of a patient with sporadic Creutzfeldt-Jakob disease. Arch Neurol (in press).
The authors reply: We detected PrPSc in muscle specimens from one fourth of patients who had died with sporadic Creutzfeldt–Jakob disease. This result may be due to limitations of the assay or may point to differences in pathogenesis between patients with PrPSc-positive and PrpSc-negative muscle specimens. Favereaux et al. raise the intriguing question of whether the presence of PrPSc in skeletal muscle might correlate with the way in which prions affect the sensory peripheral nervous system. Murine prions can invade not only sensory tracts but also arms of the sympathetic peripheral nervous system,1 and the location of immune cells in relation to sympathetic nerves appears to control the efficacy of prion neuroinvasion.2 Should the above correlations apply to sporadic Creutzfeldt–Jakob disease in humans, it would be important to identify by what means (and in which direction) prions move between the peripheral nervous system and muscle. These questions could be addressed by studying prion inoculation of suitable transgenic animal models, such as those exhibiting PrP expression restricted to the peripheral nervous system or muscle.3
Adriano Aguzzi, M.D., Ph.D.
Markus Glatzel, M.D.
Institute of Neuropathology
CH-8091 Zurich, Switzerland
adriano@pathol.unizh.ch
References
Glatzel M, Heppner FL, Albers KM, Aguzzi A. Sympathetic innervation of lymphoreticular organs is rate limiting for prion neuroinvasion. Neuron 2001;31:25-34.
Prinz M, Heikenwalder M, Junt T, et al. Positioning of follicular dendritic cells within the spleen controls prion neuroinvasion. Nature 2003;425:957-962.
Glatzel M, Flechsig E, Navarro B, et al. Adenoviral and adeno-associated viral transfer of genes to the peripheral nervous system. Proc Natl Acad Sci U S A 2000;97:442-447.