The theory that plaques in the brain cause Alzheimer’s disease has taken another hit with the discovery that it’s more to do with a lack of protein.
The plaques—a build-up of protein fragments—have been the focus of Alzheimer’s therapy since German psychiatrist Alois Alzheimer saw them in the brain of a dementia patient in 1906.
But the plaques are merely the end result of a process where the levels of amyloid-beta proteins start to reduce, say researchers at the University of Cincinnati.
The protein is a soluble—it’s dissolvable in water—but when levels start to drop, it can harden and form into the plaques seen in Alzheimer’s. People who have a build-up of plaque in their brains—but who still have healthy levels of the protein—still have good cognition and memory skills.
“Many of us accrue plaques in our brains as we age. And yet so few of us with plaques go on to develop dementia,” said researcher Alberto Espay.
Alzheimer’s drugs that have attacked the formation of plaques haven’t reversed, or even stabilised, the progress of Alzheimer’s symptoms, and those therapies that have also reduced the levels of soluble amyloid-beta proteins have quickened the patient’s mental decline.
The researchers analysed a group of patients that had a genetic mutation that increased the amount of plaques on the brain—but those who were also generating high levels of the soluble protein had normal brain functioning, and were less likely to suffer from dementia during the three years of the trial.
They think similar processes are happening in people with Parkinson’s disease and Creutzfeldt-Jakob disease. A soluble protein in the brain called alpha-synuclein can harden and form deposits known as Lewy bodies. According to the new theory, Lewy bodies don’t cause Parkinson’s but they indicate a decrease in soluble alpha-synuclein.
The researchers are now looking at the cause of the drop-off in soluble proteins and are wondering whether a toxin or virus might be the trigger.
Journal of Alzheimer’s Disease, 2022; 1: doi: 10.3233/JAD-220808