During the autopsies of eight people with a rare brain disease, doctors found something unexpected: evidence of Alzheimer's disease-like changes in the brains of six of those patients. That's especially odd, since the people were between ages 36 and 51 — very young for those changes to occur. The scientists behind the finding argue that it's the first evidence that Alzheimer's can be directly transmitted.
Other scientists are skeptical The patients in the study acquired a prion disease, caused by a misfolded protein that influences other proteins to go wrong, as a result of brain matter injections when they were younger. The study researchers, led by John Collinge, a neurologist at University College London, suggest that the injections also transmitted "seeds" for Alzheimer's. Other scientists are more skeptical.
Six of the people who were autopsied had evidence of amyloid deposits, the characteristic brain build-up associated with Alzheimer's disease. In four of those people, the amyloid plaques were widespread, according to research published in Nature. The people whose autopsies led to today's paper were among a group of people who acquired Creutzfeldt-Jakob disease from the cadaver-derived human growth hormone (hGH) they had taken decades earlier. From 1959 until 1985, children of short stature could receive injections of hGH made from the pituitary glands of corpses. Unfortunately, contaminated pituitary glands transmitted CJD, a prion disease. The disease developed for some of these patients between five and 40 years later; 450 cases have been reported as of 2012.
Prion diseases have long been considered to be analogous to Alzheimer's Both prion diseases and Alzheimer's move silently before enough brain damage occurs to cause behavioral symptoms. Prion diseases have long been considered analogous to Alzheimer's disease; in Alzheimer's, a sticky, rogue form of beta amyloid clumps in the brain — though it remains unclear whether beta amyloid is the causal agent for Alzheimer's. Previous studies in mice have shown that beta amyloid can behave like a prion when injected into genetically modified mice, "seeding" the plaques that characterize Alzheimer's. That's true even when the misfolded protein was injected into the bellies of mice rather than directly into their brains.
Since amyloid beta pathology is common and can be found in the pituitary gland, Collinge believes the abnormal protein was also harvested to make the hGH, and then seeded the infection in the patients autopsied for the report. "Given that we've looked for other explanations and not found them, we think the most likely explanation is that the growth hormone preparations with which these people were treated as children in addition to be contaminated with CJD prions, was probably also contaminated with amyloid beta seeds," Collinge said in a press conference.
"It could be that having two diseases in the brain makes Alzheimer's worse."Certain genetic risk factors increase the likelihood of developing Alzheimer's disease in midlife, but genetic testing ruled them out as an influence in today's finding. (The majority of people who develop Alzheimer's disease are 65 years old or older.) It may be that the existence of Creutzfeldt-Jakob disease sped up Alzheimer's development, said Dean Hartley, the director of scientific initiatives at the Alzheimer's Association, an advocacy group. Alzheimer's is more likely to develop in people who've had head injuries decades earlier, and also in people who have heart disease — so maybe Creutzfeldt-Jakob disease creates an environment that lets Alzheimer's develop more quickly, he said. It might be worth monitoring people who were affected by Mad Cow disease — or human spongiform encephalitis, another prion disease — to see if similar pathology is found there as well, he said.
"This may be one of the ways you can develop Alzheimer's," Hartley said. "Or it could be that having two diseases in the brain makes Alzheimer's worse." It's too soon to tell, specifically, what the finding means, he said. To try to rule out the influence of prions on Alzheimer's, the researchers on the Nature paper looked at 116 patients with other prion diseases. No other forms of prion disease were associated with beta amyloid deposits in the same way among young patients, according to the study.
Amyloid's role in Alzheimer's is contested
Amyloid build-up also exists in people who have no clinical symptoms of Alzheimer's disease, one of the reasons why its role in Alzheimer's is contested. Drug companies targeting amyloid to treat Alzheimer's disease haven't had a lot of luck, either; agents from Eli Lilly & Co, Pfizer Inc. and others have all failed in late clinical testing. Another protein, tau, also creates tangles in Alzheimer's patients — and tau deposits line up more closely with clinical symptoms. Signs of tau pathology weren't found in the patients from today's paper. Collinge believes that's because the patients died of Creutzfeldt-Jakob before full-blown Alzheimer's pathology occurred. The paper provides no evidence for that speculation, said David Allsop, a professor of neuroscience at University of Lancaster, in an emailed statement.
"It is very well known from other studies that one type of rogue protein (in this case the prion protein) can predispose to accumulation of another (in this case beta amyloid)," Allsop wrote. "There is no evidence that Alzheimer’s disease can be transmitted from one person to another, or through use of contaminated surgical instruments, and these results should be interpreted with a great deal of caution."
Allsop's concerns were echoed by other experts. "While this is a beautiful piece of investigative medicine, we have to keep the findings in context," Masud Husain, a neurology professor at the University of Oxford, said in a statement. "They concern a rare group of people who sadly developed CJD. They didn't die of Alzheimer's disease and the findings in their brains show only some of the features observed in Alzheimer patients. These results certainly do not provide sufficient evidence to believe Alzheimer's disease is a transmissible illness."
About 6 percent of the approximately 30,000 people who were treated with cadaver-derived hGH went on to develop Creutzfeldt-Jakob disease, a degenerative prion disorder. In Cruetzfeld-Jakob, a prion called PrP misfolds and becomes sticky, forming clumps. These clumps lead to the progressive brain damage seen in the disease, according to the National Institute of Neurological Disorders and Stroke.