title: Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone.
abstract: OBJECTIVE
  Growing evidence of cell-to-cell transmission of neurodegenerative disease (ND)-associated proteins (NDAPs) (ie, tau, Aβ, and α-synuclein) suggests possible similarities to the infectious prion protein (PrPsc) in spongiform encephalopathies. There are limited data on the potential human-to-human transmission of NDAPs associated with Alzheimer disease (AD) and other non-PrPsc ND.
  
  
  OBJECTIVE
  To examine evidence for human-to-human transmission of AD, Parkinson disease (PD), and related NDAPs in cadaveric human growth hormone (c-hGH) recipients.
  
  
  METHODS
  We conducted a detailed immunohistochemical analysis of pathological NDAPs other than PrPsc in human pituitary glands. We also searched for ND in recipients of pituitary-derived c-hGH by reviewing the National Hormone and Pituitary Program (NHPP) cohort database and medical literature.
  
  
  METHODS
  University-based academic center and agencies of the US Department of Health and Human Services.
  
  
  METHODS
  Thirty-four routine autopsy subjects (10 non-ND controls and 24 patients with ND) and a US cohort of c-hGH recipients in the NHPP.
  
  
  METHODS
  Detectable NDAPs in human pituitary sections and death certificate reports of non-PrPsc ND in the NHPP database.
  
  
  RESULTS
  We found mild amounts of pathological tau, Aβ, and α-synuclein deposits in the adeno/neurohypophysis of patients with ND and control patients. No cases of AD or PD were identified, and 3 deaths attributed to amyotrophic lateral sclerosis (ALS) were found among US NHPP c-hGH recipients, including 2 of the 796 decedents in the originally confirmed NHPP c-hGH cohort database.
  
  
  CONCLUSIONS
  Despite the likely frequent exposure of c-hGH recipients to NDAPs, and their markedly elevated risk of PrPsc-related disease, this population of NHPP c-hGH recipients does not appear to be at increased risk of AD or PD. We discovered 3 ALS cases of unclear significance among US c-hGH recipients despite the absence of pathological deposits of ALS-associated proteins (TDP-43, FUS, and ubiquilin) in human pituitary glands. In this unique in vivo model of human-to-human transmission, we found no evidence to support concerns that NDAPs underlying AD and PD transmit disease in humans despite evidence of their cell-to-cell transmission in model systems of these disorders. Further monitoring is required to confirm these conclusions.
authors: Center for Neurodegenerative Disease Research and Institute on Aging, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors: David J
authors: DJ
authors: Irwin
authors: Joseph Y
authors: JY
authors: Abrams
authors: Lawrence B
authors: LB
authors: Schonberger
authors: Ellen Werber
authors: EW
authors: Leschek
authors: James L
authors: JL
authors: Mills
authors: Virginia M-Y
authors: VM
authors: Lee
authors: John Q
authors: JQ
authors: Trojanowski
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002102:Cadaver; D015331:Cohort Studies; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D019382:Human Growth Hormone / Q000009:adverse effects*; D006801:Humans; D008297:Male; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology; D010300:Parkinson Disease / Q000473:pathology*; D010902:Pituitary Gland / Q000378:metabolism* / Q000473:pathology; D014481:United States; D014492:United States Public Health Service; D051844:alpha-Synuclein / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D016875:tau Proteins; D019382:Human Growth Hormone
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