Document Detail


Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone.
MedLine Citation:
PMID:  23380910     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
IMPORTANCE: 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.
DESIGN: 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.
SETTING: University-based academic center and agencies of the US Department of Health and Human Services.
PARTICIPANTS: 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.
MAIN OUTCOME MEASURES: 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 AND RELEVANCE: 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:
David J Irwin; Joseph Y Abrams; Lawrence B Schonberger; Ellen Werber Leschek; James L Mills; Virginia M-Y Lee; John Q Trojanowski
Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  JAMA neurology     Volume:  70     ISSN:  2168-6157     ISO Abbreviation:  JAMA Neurol     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-09     Completed Date:  2013-05-31     Revised Date:  2013-12-06    
Medline Journal Info:
Nlm Unique ID:  101589536     Medline TA:  JAMA Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  462-8     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / pathology*
Amyloid beta-Peptides / metabolism*
Cadaver
Cohort Studies
Databases, Factual / statistics & numerical data
Female
Human Growth Hormone / adverse effects*
Humans
Male
Neurites / metabolism,  pathology
Neurons / pathology
Parkinson Disease / pathology*
Pituitary Gland / metabolism*,  pathology
United States
United States Public Health Service
alpha-Synuclein / metabolism*
tau Proteins / metabolism*
Grant Support
ID/Acronym/Agency:
P30 AG010124/AG/NIA NIH HHS; P30 AG010124-20/AG/NIA NIH HHS; P50 NS053488/NS/NINDS NIH HHS; T32 AG000255/AG/NIA NIH HHS; T32-AG000255/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/alpha-Synuclein; 0/tau Proteins; 12629-01-5/Human Growth Hormone
Comments/Corrections

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