Alzheimer’s disease, rarely, can be cured by treatment

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AndSearchers are divided Alzheimer’s disease, the most common form of dementia, has two types. “Sporadic” cases usually occur in people over the age of 65. Rare “familial” ones involve certain mutations that run in families. Symptoms may begin as early as the patient’s 30s.

But evidence is emerging that a third, much rarer type also exists. A paper published on January 29 Nature’s medicine described five people with early-onset Alzheimer’s who were treated with human growth hormone to develop it (HGH) were given when they were children. If this indeed occurred, it would establish a third “iatrogenic” form of the disease – that transmitted through medical procedures.

The paper, by neurologist John Collins of University College London (UCL), and his colleagues build on previous research from the same group. But the story begins with a different disorder—Creutzfeldt-Jakob disease (CJD), a fatal neurodegenerative condition characterized by variants (vCJD), called “mad cow disease,” jumped from cattle to humans in the 1990s.

Stanley Prusiner, a biochemist, showed this in the 1980s CJD, and some other, related diseases, are caused not by bacteria or viruses, but by a defective form of the body’s own proteins. The defect lies in the protein’s shape rather than its chemical makeup. Before a newly made protein can do its job, it must fold itself just right. Sometimes that process goes wrong. Some misfolded proteins, called “prions” by Dr. Prusiner, can cause their other copies to misfold in turn. And too many misfolded proteins can cripple cell functions and kill them.

Like Alzheimer’s, CJD Most are either sporadic or inherited. Only 1% of cases develop infection. VCJD The 1990 outbreak was attributed to consumption of contaminated beef. But other routes are also possible. Between 1959 and 1985, about 30,000 people, mostly children, were injected around the world. HGH to increase their height. Hormones were extracted from cadaver brains. Some, it later emerged, were contaminated with CJD-Creates prions. To date, more than 200 cases CJD Those treated have been attributed.

In 2015, when examining the brains of eight people who had died this way, Dr. Collins found that four brains also had deposits of amyloid-beta, another type of protein—but not the one associated with Alzheimer’s. CJD. Because with that prion CJDAmyloid-beta can cause other copies of misshapen beta proteins to form tangled clumps in the brain. Such clumps are a hallmark of Alzheimer’s.

Dr. Collins’ team surmised that the people in question were doubly unlucky: Their hormone injections weren’t just contaminated. CJD-produces prions, but also with amyloid-beta clumps. In 2018 Dr. Colling went on to show off those untouched specimens HGH One that had been in storage since the 1980s contained amyloid-beta—and injecting the stuff into mice caused their brains to develop Alzheimer’s-like protein clumps.

Then, in 2019, a team led by Dr. Gargi Banerjee, a neurologist who also works here UCLfound that three people who received grafts of cadaveric dura mater, a thick membrane that covers the brain, suffered from cerebral amyloid angiopathy (CAA), a condition closely related to Alzheimer’s, and which also involves amyloid-beta. Dr. Banerjee argued that this was also a case of inadvertent medical transmission of misfolded proteins.

All that adds up to a highly suggestive pile of evidence. But so far, no one has found the infected patient HGH and progressed to the development of Alzheimer’s. Dr. Kalanj’s latest paper, co-authored with Dr. Banerjee, does just that. It reports eight cases referred to the National Prion Clinic UCLAnd those who had childhood HGH Medical biomarkers, blood tests and even autopsies (performed on two patients who died during the study) concluded that seven had at least some symptoms consistent with Alzheimer’s. Five had symptoms that met diagnostic criteria and that began between the ages of 38 and 55 years.

The patients were all relatively young, less likely to have sporadic Alzheimer’s. Five were genetically tested as part of their treatment; None carried the mutation known to cause the familial form of the disease. All that strongly suggests that their childhood drugs are to blame, Dr. Collins said.

“We are not suggesting for a moment that you can get Alzheimer’s disease [from other people]”He said. Although he thinks that the medical procedure caused the infection CJD The past should be looked at carefully. these days HGH It is artificially produced rather than harvested from the dead. The World Health Organization advises against human dura mater grafts. But rare cases have occurred CJD Associated with other treatments carried out in childhood.

If Dr. Collins is proven right, one question is what can be done to stop such infections in the future. Prions are solids, and can be routinely sterilized in an autoclave. Dr. Collins thinks the same is true for amyloid-beta. He and his colleagues plan to test an enzyme-detergent mixture they’ve developed for the destruction CJD To see if this also works for amyloid-beta prions.

Another is that it could have implications for treating Alzheimer’s, even in people who develop the disease spontaneously. The role that amyloid-beta plays in Alzheimer’s is not fully understood. But Dr. Collins believes his research suggests that “what’s happening in Alzheimer’s is very similar in many ways to what happens in human prion disease. CJD“This could open up new treatment possibilities for a disease that is currently incurable.

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