Isidre Ferrer
Neuropathologist and Professor Emeritus at the University of Barcelona
The study is carried out by a group of experts in prion and other neurodegenerative diseases in the UK, based on the follow-up of patients who were treated with growth hormone obtained from human cadavers according to procedures appropriate for the time. Cadaveric growth hormone treatments have been replaced years ago by synthetic growth hormone. The study is therefore based on non-repeatable historical series of patients.
The study is a manifestation of a rigorous scientific follow-up of people exposed to a treatment whose long-term complications were not foreseeable at the time the treatments were performed. The initial alarm, discovered several years ago, was the observation of the development of a transmitted prion disease in patients who had received growth hormone of cadaveric origin. About two hundred cases were described worldwide. Since, in some cases, the presence of amyloid, a protein accumulated in the brain in Alzheimer's disease, was also observed, the present study focused on the systematic analysis of patients who had received cadaveric growth hormone, with the aim of seeing whether they might have developed transmitted Alzheimer's disease as a consequence of the treatment.
The work is rigorous, although limited by the complexity of the sample. Of the eight cases described, only two have autopsy studies verifying the presence of Alzheimer's-type neuropathological changes. The diagnosis in the other cases is based on biomarker positivity during life. Even under these conditions, the brain changes revealed by autopsy are not the same as those in Alzheimer's disease, although they are very similar.
Experimental studies have shown the transmission of amyloid pathology and tau pathology (the two proteins essential for the diagnosis of Alzheimer's disease) in animal models after intracerebral inoculation (and occasionally by other routes) of samples enriched in amyloid or tau protein. These experiments are useful to show that tau can be passed from one neuron to another under physiological conditions and that abnormal tau can also be transmitted from one neuron to another, producing pathology in the recipient neuron.
The novelty of the work is to show that peripheral inoculation of suspected Alzheimer's disease material can lead to the appearance of Alzheimer's disease-like changes, including cognitive impairment, in an unknown but small proportion of patients who required this treatment many years ago.
This work, among others with similar preliminary results, raises the question of whether there may be a transmitted Alzheimer's disease in addition to the well-known sporadic and familial forms.
The limitations have already been mentioned; we are dealing with a series of non-repeatable patients, since growth hormone treatments of cadaveric origin have not been carried out for years. There is the possibility that historical cases may appear, but this form of transmission, although remote, has the irremediable tendency to become extinct.
As noted in the same paper, which is not at all alarmist, there is no evidence of any transmissible or contagious Alzheimer's disease outside the above-mentioned series and analogues.
Finally, the brain changes in patients who had treatment with growth hormone of cadaveric origin are shared with those found in Alzheimer's disease; however, it can be speculated whether this is really transmitted Alzheimer's disease or a form of neurodegenerative disease with amyloid deposits and tau deposits, unique and distinct from Alzheimer's disease in its sporadic and familial forms.
The published paper stresses the need for further scientific studies to better understand the mechanisms involved in Alzheimer's disease and other adult neurodegenerative diseases.