A coloured computed-tomography scan of a brain affected by Alzheimer’s disease.Credit: Zephyr/Science Photo Library
Researchers say they have uncovered more evidence to support a controversial hypothesis that sticky proteins that are a signature of Alzheimer’s disease can be ‘transmitted’ from person to person through certain surgical procedures.
The authors and other scientists stress that the research is based on a small number of people and is related to medical practices that are no longer used. The study does not suggest that forms of dementia such as Alzheimer’s disease can be contagious.
Still, “we’d like to take precautions going forward to reduce even those rare cases occurring”, says neurologist John Collinge at University College London who led the research, which was published1 in Nature Medicine on 29 January.
For the past decade, Collinge and his team have studied people in the United Kingdom who in childhood received growth hormone derived from the pituitary glands of cadavers to treat medical conditions including short stature. The latest study finds that, decades later, some of these people developed signs of early-onset dementia. The dementia symptoms, such as memory and language problems, were diagnosed clinically and in some patients appeared alongside plaques of the sticky protein amyloid-beta in the brain, a hallmark of Alzheimer’s disease. The authors suggest that this amyloid protein, which was present in the hormone preparations, was ‘seeded’ in the brains and caused the damage.
Contaminated hormone
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The work builds on the team’s previous studies of people who received cadaver-derived growth hormone, a practice that Britain stopped in 1985. In 2015, Collinge’s team described2 the discovery of amyloid-beta deposits in the post-mortem brains of four people who had been treated with the growth hormone. These people had died in middle-age of the deadly neurological condition Creutzfeldt-Jakob disease, which is caused by infectious, misfolded proteins called prions. The prions were present in batches of the growth hormone.
The four people analysed in that study died before clinical signs related to the amyloid build-up might have been observed. But the presence of these amyloid plaques in blood vessels in their brain suggested they would have developed a condition called cerebral amyloid angiopathy (CAA) — which causes bleeding in the brain and is often a precursor to Alzheimer’s disease.
Collinge’s team also located and studied archived batches of the cadaver-derived growth-hormone. In a 2018 study2, they found that the hormone preparation contained amyloid-beta proteins, and when the preparation was injected into mice, it led to the development of amyloid plaques and caused CAA in the animals.
This led the team to wonder whether the contaminated hormone preparations might have also led the people who received it to develop Alzheimer’s disease, in which amyloid plaques in brain tissue are thought to cause the loss of neurons and brain tissue.
In the latest study, the researchers found that 5 out of 8 people who had received the hormone treatment in childhood — but did not develop Creutzfeldt-Jakob disease — developed signs of early-onset dementia later in life, between ages 38 to 55.
Collinge’s team argues that these five people — who they studied in the clinic or through medical records and through brain scans — met the diagnostic criteria for early-onset Alzheimer’s disease. Two died during the study. Of the remaining three people, one had symptoms of mild cognitive impairment, another had possible symptoms of neurodegeneration and one did not show behavioural symptoms of Alzheimer’s.
Gene test
Early-onset Alzheimer’s is usually caused by certain genetic variants, but the researchers did not find these variants in three of the people who showed signs of Alzheimer’s and had DNA samples available for testing. “This is consistent with these patients having developed a form of Alzheimer’s disease resulting from childhood treatment with this contaminated pituitary hormone,” says Collinge. Together, the authors argue that their studies suggest that there that in rare cases, Alzheimer’s disease could be transmitted through the transfer biological material.
The small study size limits the strength of the findings, says neuroscientist Tara Spires-Jones at the UK Dementia Research Institute at the University of Edinburgh, UK. “Are the amyloid-beta seeds from the hormone treatment playing a role in the development of dementia? It’s hard to know with just eight people,” she says.
The people might also have developed dementia regardless of the hormone treatment, says neuroscientist Mathias Jucker at the German Centre for Neurodegenerative Diseases in Gottingen. “These people had many different medical conditions which could have increased the risk of developing a neurodegenerative disease like Alzheimer’s disease,” he says.
Researchers including Spires-Jones also question whether the people with dementia actually had Alzheimer’s, despite the clinical diagnoses.
“There are often errors in diagnosing the type of dementia someone has while they’re alive,” agrees neuroscience researcher Andrew Doig at the University of Manchester, UK.
From a public-health perspective, there is no need to be concerned about ‘transmissible’ dementia today, says Spires-Jones. “This treatment doesn’t exist anymore,” she says.
Despite the study’s limitations, the research furthers our understanding of neurodegenerative diseases, say scientists. “I’m glad that people are doing amazing research to help us better understand seeding of neurodegenerative disease by amyloid-beta,” says Spires-Jones.
“I think many other scientists will now look for additional evidence to explore the idea of transmissible Alzheimer’s,” says Jucker.