Scientists have been wrong about Alzheimer’s disease so far. Protein is to blame

The disease of loss

Previous research conducted in Espay’s lab suggested that Alzheimer’s disease does not arise as a direct result of atherosclerotic plaque formation. It occurs when there is not enough Aβ42.

“Aβ42 is a protein that protects our brain against a variety of toxic and infectious exposures,” Espay said. “The reaction process converts it into amyloid plaques. Amyloid plaques consist of clumped Aβ42. Once amyloid is formed, Aβ42 stops functioning (the plaques can be seen as a tombstone of Aβ42).”

In other words, Espay said, Alzheimer’s is a disease of loss: “We lose Aβ42. All people living with Alzheimer’s have low levels of Aβ42, while many of us have amyloid plaques in our brains and are cognitively normal.”

Many existing treatments for Alzheimer’s disease are based on the theory that the buildup of amyloid plaques causes the disease. However, Espay said the symptom relief seen with these drugs may be an indirect effect.

In the new study, published in the journal Brain, Espay and colleagues analyzed data from 26,000 people enrolled in 24 randomized clinical trials that examined the effects of new treatments for Alzheimer’s disease. The studies assessed cognitive impairment and differences in Aβ42 levels before and after treatment. They found that higher Aβ42 levels after treatment were associated with slower cognitive decline.

“There are two sides to every story—even the one we tell ourselves about how anti-amyloid therapies work,” Espay said. “In fact, by reducing amyloid levels, they also increase Aβ42 levels. Even if this is unintentional, it can have benefits.”

So why do some people with high levels of amyloid plaque not experience the cognitive decline associated with Alzheimer’s disease? “We found that what keeps people with amyloid plaques in a normal cognitive state is the level at which they are able to produce enough Aβ42, a protein important for brain health, to keep it at normal levels,” Espay said.

These findings could open up new possibilities for future Alzheimer’s disease therapies. “If the problem in Alzheimer’s disease is the loss of normal protein, then increasing it should be beneficial, and this study showed that this is the case,” Espay said.

Text published in the American magazine “Newsweek”. Title, lead and subtitles by the editors of “Newsweek Polska”.