'Seeds' of Alzheimer's disease might be transmissible
by Michael Smith for MedPage Today:
In rare circumstances, Alzheimer's disease might be transmissible, a study suggested.
"In addition to sporadic Alzheimer's disease and inherited or familial Alzheimer's disease, there could also be acquired forms of Alzheimer's disease," according to John Collinge, MD, of University College London, and colleagues.
But Collinge and outside experts cautioned that the research -- based on an observational study of just eight people -- is very preliminary and doesn't yet prove that the disease, or even some of its underlying pathology, can be transmitted.
In the Sept. 10 issue of Nature, Collinge and colleagues reported that autopsies of eight people who died of iatrogenic Creutzfeldt-Jakob disease (CJD) showed four had unexpectedly severe plaques of amyloid-β (Aβ), a protein associated with Alzheimer's. Another three patients had lower levels of the protein.
"The Aβ deposition in the gray matter was typical of that seen in Alzheimer's disease and Aβ in the blood vessel walls was characteristic of cerebral amyloid angiopathy," they reported. Moreover, the deposits were not located in the same places where the Creutzfeldt-Jakob prions were deposited.
The eight patients had been treated in childhood with human growth hormone derived from pituitary glands taken from cadavers, a practice that was stopped in 1985 when it was shown that some recipients were developing CJD.
"Very much to our surprise," Collinge told reporters in a telephone briefing, four showed excess amyloid-β, although they were relatively young -- ages 36 to 51 -- and had none of the genetics associated with early-onset Alzheimer's.
The findings suggested that there might be "proteopathic seeds" of Alzheimer's that can be transmitted in the same way as the prions associated with CJD and other prion diseases.
On the other hand, Collinge said, there was no evidence of the neurofibrillary tangles of tau protein, the other characteristic aspect of Alzheimer's pathology. In addition, none of the patients had developed Alzheimer's before they died of CJD, he stated.
The notion that some neurological diseases might be transmitted in the form of proteopathic seeds has been gaining traction. Indeed, amyloid-β "seeds" can lead to the accumulation of the protein in the brains of experimental mice, noted Mathias Jucker, PhD, of the University of Tübingen in Germany and Lary Walker, PhD, of Emory University in Atlanta.
In an accompanying article in Nature, they argued that the findings by Collinge and colleagues are "fresh support for this seeding concept in a clinically relevant setting."
On the other hand, the finding is likely to "result in a lot of misleading headlines," commented David Allsop, PhD, of the University of Lancaster in England.
The paper, he told the UK Science Media Centre, only shows "that some people treated with human growth hormone who subsequently went on to develop CJD also show evidence of β amyloid deposits."
"What the paper does NOT demonstrate is whether these people would have gone on to develop Alzheimer's disease had they lived long enough ... or that their pituitary β amyloid deposits were caused by contamination of growth hormone with a 'rogue' form of β amyloid," Allsop said.
It's more likely that the accumulation of the CJD proteins predisposed the patients to accumulation of another protein, in this case amyloid-β, he explained.
To assess that possibility, Collinge and colleagues looked at 116 patients with non-iatrogenic prion diseases who had undergone autopsy and found no evidence that they had excess deposits of amyloid-β.
Clinically, the finding probably has little immediate importance, Collinge said -- the study involves a treatment that is no longer performed and there is no evidence of amyloid-β transmission in other settings -- a conclusion echoed by other experts.
"With the previous mouse data, I think we can be relatively sure that it is possible to transmit amyloid pathology by the injection of human tissues which contain the amyloid of Alzheimer's disease," commented Jogn Hardy, PhD, who also is at University College London but was not involved in the study.
But that probably has no implications for most common medical procedures, such as blood transfusions, although the idea deserves systematic epidemiological investigation, he said.
Liz Coulthard, MBBS, PhD, of the University of Bristol, noted that full-blown Alzheimer's disease does not seem to be more common in people who got cadaveric growth hormone treatment, which suggests there is little "significant risk" of transmission.
"Further work is required to tease apart whether even a small proportion of Alzheimer's cases might have been transmitted," she told the media centre, adding "in the meantime, there is limited evidence on which to assess the risk from invasive surgical procedures."
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