Evidence for human transmission of amyloid-b pathology and cerebral amyloid angiopathy
More than two hundred individuals developed Creutzfeldt–Jakob disease (CJD) worldwide as a result of treatment, typically in childhood, with human cadaveric pituitary-derived growth hormone contaminated with prions. Although such treatment ceased in 1985, iatrogenic CJD (iCJD) continues to emerge because of the prolonged incubation periods seen in human prion infections. Unexpectedly, in an autopsy study of eight individuals with iCJD, aged 36–51 years, in four we found moderate to severe grey matter and vascular amyloid-b (Ab) pathology. The Ab deposition in the grey matter was typical of that seen in Alzheimer’s disease and Ab in the blood vessel walls was characteristic of cerebral amyloid angiopathy3 and did not co-localize with prion protein deposition.
In Creutzfeldt-Jakob disease and other prion diseases, the prion protein folds into an abnormal shape where the flat sheet structure replaces the helix, which means the protein can't do its normal job.
Unlike any other known protein, abnormal prion proteins are infectious. This was a radical discovery because proteins don't contain the genetic material that allows viruses and bacteria to reproduce.
These misfolded proteins induce other prions to misfold. Then these misfolded prions build up in the brain and cause the infected brain cells to die. When the infected cells die, prions are released into normal tissue and go on to infect more cells without any reaction from the immune system. Eventually, large clusters of cells die leading to the mental and behavioral symptoms of prion diseases.
Prion diseases are the only known diseases that can be sporadic, genetic or infectious.--UCSF Memory and Aging Center
iCJD. Autopsy tissue confirmed the presence of abundant Aβ plaques (cerebral amyloid angiopathy or CAA) in the brain’s parenchyma and blood vessels in a small population of people who received injections of human growth hormone extracted from cadavers (c-HGH) decades ago. The patients had all died between the ages of 36 and 51 of Creutzfeldt-Jakob Disease (CJD), caused by the injections. None had developed symptoms of Alzheimer’s disease or cerebral amyloid angiopathy (CAA). Moreover, their brains lacked the telltale tau pathology characteristic of AD.
a, Frontal cortex with widespread diffuse Ab deposition, formation of plaques, and CAA (patient no. 4).
b, c, Non-colocalized (independent) deposition of Ab and prion protein. Vessels with CAA do not entrap or co-seed prion protein. Because these deposits lack spatial overlap (non-colocalized) between CJD pathology and Aβ pathology it may support the hypothesis that the patients acquired Aβ pathology directly from the c-HGH stocks rather than as a consequence of CJD.
d, e, Adjacent histological sections stained for Ab or prion protein show clearly separated plaques of both proteins (no. 5).
f,An overlay with colour inversion of prion protein plaques highlights the separation.
g, h, Dual labelling, confocal laser microscopy shows no co-localization of parenchymal Ab plaques (no.s 5, 6) or CAA (no. 6).
i, Ab is detected in pituitary glands in patients with a high Ab load in the brain. Scale bar corresponds to 200 mm
in a, 100 mm in b–h, and 50 mm in i.
In review, we would anticipate CJD pathology but 4 of the patients also have AB deposits, another two patients have small focal AB deposits, and one had a small amount. Three of the four patients with substantial amyloidosis also had cerebral amyloid angiopathy (CAA), a condition marked by damage to brain vessels that can trigger bleeding or strokes. Genetic testing confirmed that none of the eight people contained mutations in any of 16 genes associated with early onset AD, CAA, or other neurodegenerative diseases, and none carried the ApoE4 allele.
While there is no suggestion that Alzheimer’s disease is a contagious disease and no supportive evidence from epidemiological studies that Alzheimer’s disease is transmissible, notably by blood transfusion, our findings should prompt consideration of whether other known iatrogenic routes of prion transmission, including surgical instruments and blood products, may also be relevant to Ab and other proteopathic seeds seen in neurodegenerative diseases. Ab seeds are known, like prions, to adhere to metal surfaces and to resist formaldehyde inactivation and conventional hospital sterilisation.
You can see how the article created a bit of a news bump and hysteria in some less medical or scientifically inclined news agencies.
There is no way to determine if these people would have developed Alzheimer’s disease. The protein was observed in seven of the eight brains examined.
The findings are fascinating but the sample size is way too small to draw any conclusions.
Other hallmarks of Alzheimer’s disease, such as tau protein, were not discovered in any cases. Beta-amyloid protein deposits occur in the brain as a part of aging and are not an indicative precursor for dementia or Alzheimer's disease.
We read about health literacy and initiatives to improve the understanding of complicated language reserved for discussing medicine. Patients are becoming shared-decision makers and we need to foster and clarify dialogue to improve the translation of research findings, health policy, medical education, and healthcare.
Health literacy measures the ability to comprehend, evaluate, and negotiate the data to make informed healthcare decisions. Although we tend to think of health literacy as central to societal concerns, numeracy crosses both professional and patient populations. For example, peer-reviewed clinical research often discusses risk-benefit analyses without the clarification that “risk” is defined as both benefits and harms. How do we calculate the harms of treatment to arrive at an informed clinical decision central to the patient’s best interests, values, and wishes?
How does numeracy influence standard care? What does the data show us about screening healthy individuals upstream from actual medical necessity? What do the “results” in technical medical literature really tell us? Is the message scrambled by the media? We can’t consistently blame the pharmaceutical industry. They don’t write the prescriptions—doctors do. Let’s improve numeracy in medicine.