Connecting the cause of brain diseases
Understanding how we form memories is key to treating Alzheimer’s and dementia
There’s an old saying that a crossword puzzle a day keeps your mind sharp. The newest science is starting to explain why.
As our population ages and dementia becomes more common, scientists have been racing against time to find effective treatments. Recently, we’ve started to understand how people form memories — an important step in determining how we lose them and, ultimately, how to reverse this tragic process.
We’ve found that our brains aren’t hard wired. We aren’t born knowing how to walk and talk — these things need to be learned. And the reason we’re able to learn, not just as toddlers, but throughout our lives, is due to a relatively new understanding that our brains are “plastic.”
We’ve discovered that the brain can change and be moulded to fit new circumstances. And that’s very good news for people trying to recover from strokes, brain injuries or Alzheimer’s. It even applies to autism, schizophrenia and depression — any condition that afflicts the brain.
Our nerves send signals through the brain that “carry” our thoughts and memories. The signals are controlled by connectors that can get stronger or weaker depending on hundreds of factors, genetic and environmental.
In brain diseases like Alzheimer’s, the connections are dulled. You may have heard about the telltale plaques, tangles or even brain shrinkage that can be spotted in imaging scans of a person with Alzheimer’s. Before all of those signs emerge, the very first marker is the disappearance of the nerve connectors.
There are ways to strengthen those connectors and there are ways to weaken them.
Crossword puzzles, long thought to keep the mind sharp, are a form of mental exercise that engages what we call long-term potentiation — the strengthening of the connectors.
On the flip side, chronic stress weakens those same connectors — a process called long-term depression. (However, bursts of acute stress may actually help because this engages the mind.) In a healthy brain, longterm potentiation and this “depression” in the connectors are in balance. We need to learn what throws off this balance, and how to right it.
We’re only now at the very beginning of understanding all the different ways that we can tune up the connectors in our brain that control memory. Theoretically, food and supplements could play a big role, but we don’t yet understand how to use these tools. We need to explore all of the genetic and environmental changes that can dull our connectors before we know which specific chemicals can provide an antidote.
One very promising area is the recent development of tools like gene editing, which will allow us to find the most important out of the hundreds of genes involved in brain diseases, so that we can develop treatments to shut them down without impacting other important functions.
Perhaps a more immediate next step is to fine-tune existing drugs that help to reset the balance between potentiation and depression in the connectors. Now that we know which neurotransmitters and receptors in the brain are involved, we can target them far more effectively, and should be able to develop the first truly effective Alzheimer’s treatments.
Alzheimer’s and dementia are incredibly complex diseases, and many dozens of drugs so far have failed to control them. Real breakthroughs will come because we’ve started to understand their physiology at its most basic level. The world has waited too long for good news in the fight against these heartbreaking diseases that rob people of their identity and turn loved ones into strangers. But I believe effective treatments must come from a clear understanding of disease onset and progression — and that picture is only now beginning to come into focus. Prof. Collingridge is chair of the department of physiology at U of T and a senior investigator at the Lunenfeld-Tanenbaum Research Institute of the Sinai Health System. Recently, he shared the 2016 Brain Prize (the world’s top award for brain research) for his work on longterm potentiation. Doctors’ Notes is a weekly column by members of the University of Toronto’s Faculty of Medicine. Email doctorsnotes@thestar.ca.