Pathological
deposits of Alzheimer's disease
Pathological
deposits of Alzheimer's disease and Parkinson's disease-associated proteins
(arrows) in human pituitary samples. (A= AB, the main component of Alzheimer's
disease-associated plaques, B= Tau, the main component of Alzheimer's
disease-associated tangles, C= Alpha-synuclein, the main component of Lewy
bodies in Parkinson's disease)
Mounting evidence demonstrates that the
pathological proteins linked to the onset and progression of neurodegenerative
disorders are capable of spreading from cell-to-cell within the brains of
affected individuals and thereby “spread” disease from one interconnected brain
region to another. A new study found no evidence to support concerns that these
abnormal disease proteins are “infectious” or transmitted from animals to
humans or from one person to another. The study by researchers from the
Perelman School of Medicine at the University of Pennsylvania, in conjunction
with experts from the U.S. Centers for Disease Control and the Department of
Health and Human Services, appears online in JAMA Neurology.
Cell-to-cell transmission is a potentially
common pathway for disease spreading and progression in diseases like
Alzheimer's (AD) and Parkinson's (PD) disease as well as frontotemporal lobar
degeneration (FTLD), amyotrophic lateral sclerosis (ALS) and other related
disorders. It appears that misfolded proteins spread from one cell to another
and that the affected neurons become dysfunctional, while these toxic proteins
go on to damage other regions of the brain over time.
"By interrogating an existing database
with information on a cohort of well-characterized patients, we were able to
determine that there is no evidence suggesting the pathology of Alzheimer’s or
Parkinson’s can transmit between humans,"
said senior author John Q. Trojanowski, MD, PhD, professor of Pathology
and Laboratory Medicine and co-director of the Penn Center for
Neurodegenerative Disease Research. "We can now redouble efforts to find
treatments, via immunotherapies or other approaches to stop the spreading of
these toxic proteins between cells."
In order to verify whether such proteins
could potentially be carried from person to person, the team of researchers
analyzed data from an existing cohort of patients who had received human growth
hormone (hGH) from cadaveric pituitary glands via a national program, as a
beneficial treatment for stunted growth, before synthetic hGH was available.
Nearly 7,700 patients were treated with cadaver-derived hGH (c-hGH) in the US
between 1963 and 1985. In the mid-1980s, more than 200 patients worldwide who
had received c-hGH inadvertently contaminated with prion proteins from affected
donor pituitary tissue went on to develop an acquired form of Creutzfeldt-Jakob
disease (CJD), a rare, degenerative, invariably fatal brain disorder caused by
pathological prion proteins that also are the cause of Mad Cow disease. Since
then, the cohort has been followed to track any additional cases of CJD, with
extensive medical histories for patients over the 30+ years since the c-hGH
therapy was stopped after the link to CJD was discovered in 1985.
In this current study, researchers looked for
signs of an elevated risk of AD, PD, FTLD or ALS among this group and found
that none of the c-hGH recipients developed AD, PD or FTLD. The team did
identify three ALS cases of unclear significance, given that no traces of ALS
disease proteins (TDP-43, FUS and Ubiquilin) were found in human pituitary
glands, despite the presence of pathological AD (tau, Aβ) and PD
(alpha-synuclein) proteins. This clarified that c-hGH recipients were most
likely exposed to these neurodegenerative disease proteins linked to AD, PD and
FTLD but this did not result in transmission of disease from person to person.
"This cohort is an invaluable resource
and should continue to be followed, especially as we rapidly increase our
understanding of disease progression in neurodegenerative conditions,"
said David Irwin, MD, lead author, and fellow in the Center for
Neurodegenerative Disease Research and the department of Neurology in the
Perelman School of Medicine.
Source: Penn Medicine
No comments:
Post a Comment