Alzheimer’s protein may help brain fight infection _ science _ aaas

The classic villain in Alzheimer ’s disease is ß amyloid, a protein fragment that can misfold and form sticky plaques around neurons in the brain. Is there a treatment for alzheimer’s disease Now, a new study in mice and worms supports a controversial hypothesis that the plaques may not be all bad. Alzheimer’s disease association ß amyloid ’s tendency to choke neurons could be linked to an ancient evolutionary mission to protect the brain from pathogens, the authors say.

Some say the work could open new avenues for treating and preventing the deadly degenerative disease, but many in the Alzheimer ’s field remain skeptical of the research, which used animals genetically modified to make human ß amyloid. Alzheimer’s disease video Although the new data are “fascinating,” they “remain very contrived in the sense that they don’t bear a direct relationship to what we see in the human condition,” says Colin Masters, a neuroscientist at the University of Melbourne in Australia.

ß-amyloid deposits can damage many organs besides the brain, including the heart, liver, and kidneys, says neuroscientist Rudolph Tanzi of Massachusetts General Hospital (MGH) in Boston, a leader of the new study. Late onset alzheimer’s disease That raises a puzzling question: If the protein is so bad, why do animals dating back to the 400-million-year-old coelacanth fish taxon produce it? Among mammals, the gene that codes for the protein from which ß amyloid derives is “almost identical” across species, says Claudio Soto Jara, a neuroscientist at the University of Texas, Houston. Alzheimer’s disease symptoms and treatment Dogs, for example, develop Alzheimer-like ß-amyloid plaques and symptoms of dementia as they age.

Six years ago, Tanzi and neuroscientist Robert Moir, also at MGH, decided to test a hunch that ß amyloid behaves similarly to a class of proteins with well-known beneficial properties, called antimicrobial peptides, or AMPs. Alzheimer’s disease causes Some AMPs also form fibers around cells, but they use them to trap and kill microbes throughout the body. First signs of alzheimer’s disease To see whether ß amyloid was similarly lethal, the team tested it in lab dishes on a suite of different microbes, including the yeast Candida albicans , and bacteria like Escherichia coli and several different strains of Streptococcus. Alzheimer’s disease brain The maligned protein was just as toxic to many pathogens as the AMPs. Alzheimer’s disease prognosis Indeed, against some microbes, it was 100 times more lethal than penicillin, Moir says.

Moir and Tanzi hypothesized that ß amyloid has an ancient role in the body protecting against foreign invaders. What are the physical symptoms of alzheimer disease Few took them seriously, however, because the molecule hadn ’t been shown to kill microbes in living animals. Sporadic alzheimer’s disease They also encountered resistance, Moir says, from those who support the dominant approach to developing Alzheimer ’s drugs. What are the symptoms of alzheimer’s disease For decades, pharmaceutical companies have treated ß amyloid as a “freak” with no beneficial purpose, and focused nearly all their energies on finding drugs to eliminate the molecules, he says. Sign of alzheimer’s disease In these companies’ view, according to Moir, “everything it does is bad—all you ’ve got to do is get rid of it and you ’ll be hunky-dory.”

The new study is a “proof of concept” in animals that ß amyloid does indeed protect against pathogens, Tanzi says. Protein involved in alzheimer’s disease First, the researchers used mice that had been genetically modified to produce excess amounts of the human version of ß amyloid—a common Alzheimer ’s disease model. Alzheimer disease definition psychology Then they injected the rodents ’ brains with Salmonella bacteria to cause an infection and waited to see whether the mice making the extra amyloid did better than controls at fighting off the microbes. How do you get alzheimer’s disease All the mice died within 96 hours, but those with human amyloid lost less weight, had fewer bacteria in their brains, and lived up to roughly 30 hours longer than the control mice, the team reports today in Science Translational Medicine.

Next, the scientists tested their hypothesis in the widely studied worm Caenorhabditis elegans, and found that a strain genetically engineered to produce excess amyloid in their guts survived up to 3 days longer after an exposure to Salmonella and yeast than typical worms.

Taken together, the animal data suggest that a range of different microbes can induce amyloid plaques to form, Tanzi says. Alzheimer’s disease information Most striking, he says, are results from mice engineered to make human amyloid ß. History of alzheimer’s disease The rodents would not normally develop amyloid plaques until late in life, but young ones formed the sticky deposits immediately after the Salmonella injection, providing evidence that the infection and plaques were linked, Tanzi says.

The fact that amyloid can behave like an antimicrobial peptide is “really surprising,” and could be a new angle for the Alzheimer ’s field, Soto Jara says. Stages of alzheimer disease pdf Still, he says, the work is “highly speculative at this point.”

Tanzi acknowledges that. Characteristics of alzheimer’s disease “We are not saying that any of these microbial pathogens cause Alzheimer ’s disease” in people, he notes. Prognosis of alzheimer’s disease To investigate that, scientists will need to examine the brain tissue of many people who have died of Alzheimer ’s, looking for different pathogens and whether the microbes are surrounded by amyloid plaques, he says. Alzheimer’s disease definition Although dozens of previous studies have hunted for infectious agents that could trigger Alzheimer’s, they haven’t been systematic enough to identify a culprit, Tanzi says. Alzheimer’s disease is caused by A new, half-million-dollar project sponsored by the Cure Alzheimer ’s Fund will soon take on that challenge, he adds.

If scientists determine that certain microbes do trigger amyloid deposition in human brains, Tanzi suggests it might be possible to develop antibodies that target them and avert that reaction. Diagnosis of alzheimer’s disease In addition, if ß amyloid does play an important protective role in the brain, it might make sense to treat it more like cholesterol—which is needed by all cells but dangerous in high levels—than something that needs to be completely eliminated, Tanzi says: “Slow it down, yes—but don ’t wipe it out.”