麻豆传媒

Alzheimer's disease appeared to be transmissible under rare conditions, according to new research.

Five patients treated with human growth hormone from cadaveric pituitary glands when they were children subsequently developed early dementia or biomarker changes consistent with Alzheimer's disease, reported John Collinge, MD, of University College London in England, and co-authors in .

Four of these patients were between ages 38 and 49 when their Alzheimer's symptoms started; the fifth was 55. Two had biomarker changes that supported an Alzheimer's diagnosis. Two did not have molecular biomarker testing but showed progressive brain atrophy on imaging, and one had Alzheimer's pathology detected at autopsy.

The findings do not mean that Alzheimer's can be transmitted between people during daily activities or routine medical care, Collinge emphasized.

"The patients we have described were given a specific and long-discontinued medical treatment, which involved injecting patients with material now known to have been contaminated with disease-related proteins," Collinge said in a press briefing.

"However, the recognition of transmission of amyloid-beta pathology in these rare situations should lead us to review measures to prevent accidental transmission via other medical or surgical procedures, in order to prevent such cases occurring in the future," he added.

Between 1959 and 1985, cadaver-derived human growth hormone was used to treat young patients for pituitary insufficiency. The product was withdrawn after some patients received prion-contaminated cadaveric growth hormone and (CJD) in the U.K., the U.S., and other countries.

In 2015, Collinge and co-authors reported that some of those who died of iatrogenic CJD had amyloid-beta pathology at autopsy. Whether these people also had Alzheimer's symptoms wasn't known, because CJD -- a universally fatal prion disease that progresses rapidly -- might have masked any symptoms.

A few years later, Collinge and colleagues tested old vials of the cadaveric growth hormone for amyloid and tau proteins implicated in Alzheimer's disease; they showed that samples of the hormone could seed amyloid-beta pathology in mice.

In the current study, the researchers concluded -- based on multiple factors, including the unusually young age when cognitive symptoms started and the lack of other possible explanations such as Alzheimer's-related genes -- that contaminating amyloid-beta seeds in the growth hormone preparations triggered a prolonged pathogenic cascade that eventually manifested as Alzheimer's disease.

"On the one hand, it is prudent to consider these conclusions with a measure of skepticism," observed Mathias Jucker, PhD, of the University of Tübingen in Germany, and Lary Walker, PhD, of Emory University in Atlanta, in an . "The cases presented are diverse and complicated; the individuals had undergone a variety of medical interventions for various disorders earlier in life, and it is difficult to exclude a contribution of these circumstances to the complex disease phenotypes that appeared many years later," they noted.

But there's good reason to take these findings seriously, Jucker and Walker said.

"Only individuals who received cadaveric growth hormone prepared in a specific way (the modified Wilhelmi method) developed the features of Alzheimer's disease," they pointed out. "Prior investigations had shown that the Wilhelmi protocol does not eliminate contaminating prions and amyloid-beta seeds from pituitary extracts; persons treated with growth hormone prepared using the more stringent size-exclusion chromatography purification method appear not to have been at increased risk of iatrogenic Alzheimer's disease."

The evidence showing amyloid-beta pathology could be transmitted from old cadaveric growth hormone samples to mice also supported the new findings, they added.

From a practical standpoint, the report underscored the importance of informed caution when preparing surgical instruments, handling tissues, or using therapeutic biologics derived from human sources, the editorialists noted.

"From a theoretical standpoint, the findings lend new support to the hypothesis that Alzheimer's disease bears fundamental etiologic similarities to prion diseases," they wrote.

The current report from Collinge and co-authors was based on eight cases referred to University College London Hospital's National Prion Clinic. All patients had been treated with cadaveric growth hormone in childhood decades earlier. None had CJD. Besides the five cases diagnosed with Alzheimer's, one patient had mild cognitive impairment, one had subjective cognitive symptoms, and one was asymptomatic.

In total, more than 1,800 people in the U.K. received cadaveric growth hormone from 1959 to 1985. , nearly 7,700 children were treated with pituitary human growth hormone under the National Hormone and Pituitary Program (NHPP) from 1963 to 1985. In 1977, the NHPP started a safer purification method and later fully switched to recombinant human growth hormone.

Current treatment includes synthetic growth hormone, so cases like this are no longer possible, the researchers said. No other cases of iatrogenic Alzheimer's from any other medical or surgical procedures have been reported, they added.

"We think from a public health point of view, this is probably going to be a relatively small number of patients," Collinge said. "However, the implications of this paper, we think, are broader with respect to disease mechanisms, that it looks like what's going on in Alzheimer's disease is very similar in many respects to what happens in the human prion disease like CJD -- the propagation of these abnormal aggregates of misfolded proteins or misshapen proteins, which propagate and spread in the brain."

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