Amyloid beta pathology in the grey matter and blood vessel walls
characteristic of Alzheimer's disease (AD) and the related cerebral
amyloid angiopathy (CAA) is observed in the brains of deceased
patients who acquired Creutzfeldt-Jakob disease (CJD) following
treatment with prion-contaminated human growth hormone.
Although there is no evidence that human prion disease, AD or
CAA is contagious (spread from person to person by direct contact),
the study of eight patients suggests that amyloid beta (the
peptides that form the main components of the amyloid plaques found
in the brains of patients with AD) may potentially be transmissible
via certain medical procedures.
Human transmission of prion disease has occurred as a result of
various medical procedures (iatrogenic transmission), with
incubation periods that can exceed five decades.
One such iatrogenic route of transmission was via the treatment
in the UK of 1,848 persons of short stature with human growth
hormone (HGH) extracted from cadaver-sourced pituitary glands, some
of which were inadvertently prion-contaminated. The treatments
began in 1958 and ceased in 1985 following reports of CJD among
recipients. By the year 2000, 38 of the patients had developed CJD.
As of 2012, 450 cases of iatrogenic CJD have been identified in
countries worldwide after treatment with cadaver-derived HGH and,
to a lesser extent, other medical procedures, including transplant
and neurosurgery.
John Collinge, Sebastian Brandner and colleagues at UCL
(University College London) conducted autopsy studies, including
extensive brain tissue sampling, of eight UK patients aged 36-51
with iatrogenic CJD. The authors show that in addition to prion
disease in all eight brains sampled, six exhibited some degree of
amyloid beta pathology (four widespread) and four of these had some
degree of CAA. Such pathology is rare in this age range and none of
the patients were found to have mutations associated with
early-onset AD.
There were no signs of the tau protein pathology characteristic
of AD, but the full neuropathology of AD could potentially have
developed had the patients lived longer. The authors examined a
cohort of 116 patients with other prion diseases and found no
evidence of amyloid beta pathology in the brains of patients of
similar age range or a decade older who did not receive HGH
treatment.
The study suggests that healthy individuals exposed to
cadaver-derived HGH may be at risk of iatrogenic AD and CAA, as
well as iatrogenic CJD, as they age. Further research is needed to
better understand the mechanisms involved, but it seems likely
that, as well as prions, the pituitary glands used to make the HGH
contained the amyloid beta seeds that caused the amyloid beta
pathology observed.
The results should prompt investigation of whether other known
iatrogenic routes of prion transmission, including surgical
instrument use and blood transfusion, could also be relevant to the
transmission of AD, CAA and other neurodegenerative diseases.
Professor Collinge, Director of the MRC Prion Unit at the UCL
Institute of Neurology, said: "Our findings relate to the specific
circumstance of cadaver-derived human growth hormone injections, a
treatment that was discontinued many years ago. It is possible our
findings might be relevant to some other medical or surgical
procedures, but evaluating what risk, if any, there might be
requires much further research. Our current data have no bearing on
dental surgery and certainly do not argue that dentistry poses a
risk of Alzheimer's disease."
Professor Mike Hanna, Director of the UCL Institute of
Neurology, said: "This is potentially very important research from
the UCL Institute of Neurology Prion research Group lead by John
Collinge and Sebastian Brandner. It could inform our understanding
of the molecular mechanisms leading to Alzheimer's disease and will
enable new programmes of world leading research in Dementia at the
Institute of Neurology, Queen Square."
The paper, Evidence for human transmission of amyloid-? pathology and cerebral
amyloid angiopathy, is published inNature.