Clues to How Alzheimer’s Damages the Brain
Fortunately, neither this scientific investigation nor any other offers convincing evidence that you can “catch” Alzheimer’s disease. However, the Nature paper offers support for an evolving theory about how this and perhaps other devastating forms of dementia spread throughout the brain. Conceivably, this information could help drug developers find ways to defeat the disease.
Good intentions gone wrong
This story begins with a well-intended treatment that went terribly wrong. In the late 1950s, physicians began giving shorter-than-average children and adolescents injections of human growth hormone to increase their height. The hormone had been extracted from the pituitary glands of cadavers.
The practice was ended in 1985 when reports emerged that some of the recipients of the hormone injections had developed Creutzfeldt–Jakob disease, a rare and fatal brain disorder that causes dementia and loss of muscle coordination.
Proteins are formed when building blocks called amino acids are joined together in a very specific order. These long pieces of protein then “fold” into a 3-D structure. If the protein becomes “misfolded,” it can act abnormally and become destructive.
The role of the prion protein
Scientists think Creutzfeldt–Jakob disease is caused by an abnormally shaped protein known as the prion protein. All humans have the gene for the prion protein. Creutzfeldt–Jakob disease is caused by an abnormally folded form of this prion protein.
What is extraordinary about the prion protein is that when it misfolds it causes other nearby prion proteins to misfold, essentially producing a chain reaction. It is this chain reaction that is the mechanism by which Creutzfeldt–Jakob disease spreads through the brain.
Creutzfeldt-Jakob disease can be inherited and can occur spontaneously in humans. It can also be passed as an infection from human to human. Apparently, some of the pituitary glands used to make batches of the growth hormone injections contained the abnormal prion proteins and these infected the unfortunate recipients.
As of 2012, Creutzfeldt–Jakob disease was known to have been transmitted to at least 450 people worldwide through hormone injections, corneal transplants, transplants of the tissue lining the spinal cord, and the use medical devices tainted with the protein and used in various medical procedures, such as organ transplants and brain surgery.
In the 2015 Nature study, doctors from the National Hospital for Neurology and Neurosurgery in London, England, performed autopsies on the brains of eight people who received human growth hormone treatments and subsequently died of Creutzfeldt–Jakob disease. The patients’ ages at death ranged from 36 to 51. The researchers were surprised to discover that four of the brains had significant accumulations of the amyloid-beta protein.
The deposition of beta-amyloid in the brain is a hallmark of Alzheimer’s disease. Levels of amyloid in the four brains were deemed moderate to severe, typical of a patient with Alzheimer’s disease. Three other brains had lesser amounts of beta-amyloid (mostly on the walls of arteries), while just one of the eight patients had none.
The authors considered the possibility that the prions transmitted in the hormone injection caused an injury in the brain that triggered the formation of amyloid-beta.
However, a separate examination of 116 patients with Creutzfeldt-Jakob disease not caused by hormone injections found no evidence of Alzheimer’s disease. Instead, the investigators suspect that some of the pituitary glands used to make the growth hormone treatments may have contained beta-amyloid, which was then “seeded” into the children who received the injections.
Since beta-amyloid is suspected to play a critical role in Alzheimer’s disease, this study may have uncovered the first evidence that the disease could be transmitted from one human to another by way of a medical procedure, just as prions are known to be passed from person to person.
Reasons for caution
Earlier studies involving lab animals, including marmosets (a type of small primate) and mice, have already demonstrated that amyloid-beta can be seeded into the brain.
The Nature study’s authors argue that this animal research and their investigation demonstrate that there’s a plausible explanation for how beta-amyloid seeds might be transported from one brain to another. They speculate that as other people who received the growth hormone injections age, they may be at risk for early-onset Alzheimer’s disease.
However, there are a number of reasons to view this study with a cautious eye. For starters, the researchers only examined the brains of a small number of patients; studies that include larger numbers of patient are more reliable, since their results are less likely to have occurred due to chance.
More importantly, some individuals develop deposits of beta-amyloid during their 30s and 40s so the elevated levels identified in several of the patients in the Nature study may simply have occurred as a result of aging.
What’s more, even though the subjects in the study had beta-amyloid in their brains, they weren’t displaying symptoms of Alzheimer’s disease. And finally, none of the brains studied had neurofibrillary tangles, the other protein abnormality seen in people with Alzheimer’s disease.
The authors of the report note that the individuals in the study were relatively young, raising the possibility that they might have developed tangles eventually if they hadn’t died of Creutzfeldt–Jakob disease.
The authors of the Nature paper argue that their findings should spur hospitals and other healthcare providers to take additional steps to ensure that patients aren’t exposed to prions and Alzheimer’s disease-promoting proteins such as amyloid-beta during surgery and when receiving blood transfusions. They note, for example, that prions and amyloid-beta seeds adhere to metal surfaces, making it more difficult to sterilize surgical instruments.
Yet the risk of transmitting a prion disease such as Creutzfeldt–Jakob disease is exceedingly low. Moreover, if receiving blood from a donor exposed people to beta-amyloid and other potential seeds for Alzheimer’s disease, then people who have received frequent transfusions would be more likely to develop dementia. But studies have shown this is not the case.
The bottom line
Here’s the key takeaway message from this study: Despite what overly enthusiastic headline writers may have splashed over newspapers and websites, there is absolutely no evidence that Alzheimer’s disease is contagious.
As a side note, there is interest among some scientists in a potential link between Alzheimer’s disease and certain bacterial infections, which could theoretically harm neurons by promoting inflammation. But the association between Alzheimer’s disease and infections remains speculative and needs more study.
The true importance of this research may be that it provides us with additional insight as to how this devastating form of dementia spreads in the brain. We know that Alzheimer’s disease begins in one brain region, then gradually spreads to others.
One possibility suggested by this study and others is that amyloid proteins behave like prions, reproducing themselves by causing nearby proteins to misfold, and in doing so moving from one neuron to the next, slowly spreading damage throughout the brain and killing brain cells in the process.
Earlier studies suggest that misfolded tau proteins spread through the brain in a similar fashion. Understanding how and why normal, healthy proteins misfold could lead scientists to develop drugs that block the process, which could help scientists develop medications that stop or slow the spread of Alzheimer’s disease, as well as Creutzfeldt–Jakob disease and other prion diseases.