Prion-like transmission of neurodegenerative pathology stirs concern

Recent developments regarding the nature of transmissible pathologic proteins in a variety of common neurodegenerative diseases have started to cause clinicians and public health experts to wonder if there is cause for concern.

A group from the National Hospital for Neurology & Neurosurgery at Queen Square, London, recently published a study presenting evidence that Alzheimer’s disease may have transmissible properties similar to traditionally regarded prion diseases such as Creutzfeldt-Jakob disease (Nature. 2015 Sep 10;525:247-50. doi:10.1038/nature15369). This conclusion was based upon the observation of cerebral and vascular amyloid-beta deposition in several patients who had received cadaveric growth hormone extracts ranging from 19 to 39 years earlier and who developed iatrogenic Creutzfeldt-Jakob disease (CJD). Amyloid deposition was also identified in the pituitary glands of patients with amyloid-beta pathology also felt to be iatrogenically transmitted.

This is not the first time, however, that analogies have been drawn between neurodegenerative diseases and prion-related diseases. Perhaps inspired by the evident connectivity of affected upper and lower motor neuronal populations in amyotrophic lateral sclerosis, previous investigators have sought cell-to-cell transmission of neurodegenerative pathology and have demonstrated this for amyloid as well as tau species in Alzheimer’s disease, and for synuclein species in Parkinson’s disease.

A recent article by Dr. Stanley Prusiner of the University of California, San Francisco, and his colleagues presented evidence that brain extracts from patients with multiple system atrophy (MSA) transmitted the characteristic MSA alpha-synuclein aggregates in the brains of transgenic mice as well as in cultured human embryonic kidney cells (Proc Natl Acad Sci U S A. 2015 Aug 31. doi:10.1073/pnas.1514475112).

An emerging theme from these recent and prior studies is that neurodegenerative diseases behave a lot like prion diseases, and although they follow a much slower time course, may spread through synaptic pathways as well as between people through prion-like mechanisms. CJD, while transmissible, is not “contagious,” and public messaging should draw this distinction in regard to neurodegenerative diseases. Nonetheless, further research is urgently needed given the implications of this work. Dr. Prusiner and his associates concluded, for example, that deep brain stimulation electrodes and related equipment should not be reused from Parkinson’s disease patients for fear of spreading the synucleinopathy from one person to another. Should there be restrictions with regard to any form of tissue transplantation or blood transfusion from patients with Parkinson’s disease or Alzheimer’s disease? Questions such as these need further clarification, and given the prevalence of these procedures, such research should be highly prioritized.

Dr. Caselli is professor of neurology at the Mayo Clinic, Scottsdale, Ariz. He also serves there as associate director and clinical core director of the Alzheimer’s Disease Center.

Recent developments regarding the nature of transmissible pathologic proteins in a variety of common neurodegenerative diseases have started to cause clinicians and public health experts to wonder if there is cause for concern.

A group from the National Hospital for Neurology & Neurosurgery at Queen Square, London, recently published a study presenting evidence that Alzheimer’s disease may have transmissible properties similar to traditionally regarded prion diseases such as Creutzfeldt-Jakob disease (Nature. 2015 Sep 10;525:247-50. doi:10.1038/nature15369). This conclusion was based upon the observation of cerebral and vascular amyloid-beta deposition in several patients who had received cadaveric growth hormone extracts ranging from 19 to 39 years earlier and who developed iatrogenic Creutzfeldt-Jakob disease (CJD). Amyloid deposition was also identified in the pituitary glands of patients with amyloid-beta pathology also felt to be iatrogenically transmitted.

This is not the first time, however, that analogies have been drawn between neurodegenerative diseases and prion-related diseases. Perhaps inspired by the evident connectivity of affected upper and lower motor neuronal populations in amyotrophic lateral sclerosis, previous investigators have sought cell-to-cell transmission of neurodegenerative pathology and have demonstrated this for amyloid as well as tau species in Alzheimer’s disease, and for synuclein species in Parkinson’s disease.

A recent article by Dr. Stanley Prusiner of the University of California, San Francisco, and his colleagues presented evidence that brain extracts from patients with multiple system atrophy (MSA) transmitted the characteristic MSA alpha-synuclein aggregates in the brains of transgenic mice as well as in cultured human embryonic kidney cells (Proc Natl Acad Sci U S A. 2015 Aug 31. doi:10.1073/pnas.1514475112).

An emerging theme from these recent and prior studies is that neurodegenerative diseases behave a lot like prion diseases, and although they follow a much slower time course, may spread through synaptic pathways as well as between people through prion-like mechanisms. CJD, while transmissible, is not “contagious,” and public messaging should draw this distinction in regard to neurodegenerative diseases. Nonetheless, further research is urgently needed given the implications of this work. Dr. Prusiner and his associates concluded, for example, that deep brain stimulation electrodes and related equipment should not be reused from Parkinson’s disease patients for fear of spreading the synucleinopathy from one person to another. Should there be restrictions with regard to any form of tissue transplantation or blood transfusion from patients with Parkinson’s disease or Alzheimer’s disease? Questions such as these need further clarification, and given the prevalence of these procedures, such research should be highly prioritized.

Dr. Caselli is professor of neurology at the Mayo Clinic, Scottsdale, Ariz. He also serves there as associate director and clinical core director of the Alzheimer’s Disease Center.

Recent developments regarding the nature of transmissible pathologic proteins in a variety of common neurodegenerative diseases have started to cause clinicians and public health experts to wonder if there is cause for concern.

A group from the National Hospital for Neurology & Neurosurgery at Queen Square, London, recently published a study presenting evidence that Alzheimer’s disease may have transmissible properties similar to traditionally regarded prion diseases such as Creutzfeldt-Jakob disease (Nature. 2015 Sep 10;525:247-50. doi:10.1038/nature15369). This conclusion was based upon the observation of cerebral and vascular amyloid-beta deposition in several patients who had received cadaveric growth hormone extracts ranging from 19 to 39 years earlier and who developed iatrogenic Creutzfeldt-Jakob disease (CJD). Amyloid deposition was also identified in the pituitary glands of patients with amyloid-beta pathology also felt to be iatrogenically transmitted.

This is not the first time, however, that analogies have been drawn between neurodegenerative diseases and prion-related diseases. Perhaps inspired by the evident connectivity of affected upper and lower motor neuronal populations in amyotrophic lateral sclerosis, previous investigators have sought cell-to-cell transmission of neurodegenerative pathology and have demonstrated this for amyloid as well as tau species in Alzheimer’s disease, and for synuclein species in Parkinson’s disease.

A recent article by Dr. Stanley Prusiner of the University of California, San Francisco, and his colleagues presented evidence that brain extracts from patients with multiple system atrophy (MSA) transmitted the characteristic MSA alpha-synuclein aggregates in the brains of transgenic mice as well as in cultured human embryonic kidney cells (Proc Natl Acad Sci U S A. 2015 Aug 31. doi:10.1073/pnas.1514475112).

An emerging theme from these recent and prior studies is that neurodegenerative diseases behave a lot like prion diseases, and although they follow a much slower time course, may spread through synaptic pathways as well as between people through prion-like mechanisms. CJD, while transmissible, is not “contagious,” and public messaging should draw this distinction in regard to neurodegenerative diseases. Nonetheless, further research is urgently needed given the implications of this work. Dr. Prusiner and his associates concluded, for example, that deep brain stimulation electrodes and related equipment should not be reused from Parkinson’s disease patients for fear of spreading the synucleinopathy from one person to another. Should there be restrictions with regard to any form of tissue transplantation or blood transfusion from patients with Parkinson’s disease or Alzheimer’s disease? Questions such as these need further clarification, and given the prevalence of these procedures, such research should be highly prioritized.

Dr. Caselli is professor of neurology at the Mayo Clinic, Scottsdale, Ariz. He also serves there as associate director and clinical core director of the Alzheimer’s Disease Center.