National Post (National Edition)
HOW DOES THE BRAIN BREAK?
ALMOST ONE MILLION CANADIANS LIVE WITH ALZHEIMER'S
Scientists have made a lot of progress when it comes to understanding Alzheimer's disease since it was first described in 1906. But the disease is complex, highlighted by the fact that more than a century of dedicated research and billions of dollars still hasn't resulted in a cure. Here's what we know about the science behind the disease, why drug trials continue to fail and what scientists still have left to discover.
WHAT HAPPENS TO YOUR BRAIN WHEN YOU HAVE ALZHEIMER'S DISEASE?
In the simplest terms, Alzheimer's is a neurodegenerative disease that impacts memory, thinking and behaviour.
“Neurodegeneration is a general term that we use when cells and their connections don't work properly, which means there isn't proper communication between brain cells,” says Dr. Jack Jhamandas, professor at the University of Alberta. “This affects basic physiological functions such as memory and the ability to store and receive information which is what happens when someone has Alzheimer's.”
When it comes to the actual cause of this neurodegeneration, science suggests there are three main culprits. The first is the amyloid protein which builds up to form toxic plaques in the brain. The second disease hallmark is neurofibrillary tangles — abnormal accumulations of the tau protein in the brain. The latest research is also pointing to inflammation in brain cells and the role it plays in failing to stop toxins from entering the brain. The end result: cells stop functioning, they start to die, and the brain shrinks.
The question then becomes what causes these proteins to build up and the brain to become inflamed in the first place. While a small number of cases — roughly five per cent — can be explained by genetic predisposition, scientists don't fully understand what catalyzes these events in the remaining 95 per cent of Alzheimer's cases.
WHAT IS THE DIFFERENCE BETWEEN ALZHEIMER'S DISEASE AND DEMENTIA?
Dementia is the general term used to describe a range of brain disorders that impact memory, thinking and behaviour. Alzheimer's disease is the most common form, accounting for around 80 per cent of all dementia cases. There are many other forms of dementia, including vascular dementia which is the result of small strokes in the brain, and Lewy body dementia which often affects mobility.
A small number of cases — roughly five per cent — can be explained by genetic predisposition
WHY IS YOUR MEMORY AFFECTED WHEN YOU HAVE ALZHEIMER'S?
Amyloid protein plaques tend to be deposited in the cortex and hippocampus regions of the brain, both of which are important for learning and memory, although it's not clear why this part of the brain is targeted. As the disease progress, amyloid plaques and tau proteins begin to build up in other parts of the brain which impacts areas responsible for things such as language and behaviour.
Even though people living with Alzheimer's exhibit signs of forgetfulness, memories can still exist somewhere in the brain, they're just difficult to retrieve.
“Memories are stored in our synaptic connections and to retrieve them our brain has to release the correct chemical to allow communication to happen,” says Dr. Jane Rylett, professor and scientist at Western University and scientific director of CIHR Institute of Aging. “When someone has Alzheimer's, sometimes this works and sometimes it doesn't.”
Rylett says in early stages of the disease many people are still able to retrieve memories but as the disease progresses these connections break down and eventually memories can be lost.
WHY HAS FINDING A CURE FOR ALZHEIMER'S BEEN SO CHALLENGING?
No clinical trials have found a cure for Alzheimer's, but it's not for lack of trying. There have been countless attempts with a focus on two main areas of drug research. The first are drugs that bind to and destroy amyloid plaques or prevent plaques from forming in the first place. The second route has taken a similar approach by targeting the tau protein responsible for forming tangles.
So far, nothing has worked. According to both Rylett and Jhamandas, perhaps this is because the brain has undergone years of change before Alzheimer's symptoms actually appear. In other words, the brain might be too damaged by the time a drug is given to actually reverse or prevent any impairments.
“The initiating event happens early on, maybe even decades before someone shows up to the doctor's office with symptoms,” says Rylett.
“That's where the problem is — we don't know what the real underlying initiating events are or when they start, which makes it difficult to devise treatments. In a sense, you're trying to work backwards; you don't know who the affected individuals will be because it could be 10 to 20 years before they start to show symptoms.”
Although there is no cure, drugs do exist to reduce symptoms in the short term. These drugs fall into two broad categories: acetylcholinesterase inhibitors and memantine. The former boosts levels of the chemical messenger acetylcholine, which plays an important role in memory and exists in abnormally low levels in people living with Alzheimer's.
Memantine is a treatment used in later stages of the disease and regulates glutamate, another important chemical messenger impaired when someone has Alzheimer's.
You don't know who the affected individuals will be because it could be 10 to 20 years before they start to show symptoms
WHERE IS RESEARCH HEADED?
Research has shown that exercise, a healthy diet and social interaction are all associated with better brain health and lower risk of developing Alzheimer's. But there are still many unknowns and scientists continue to study the exact cause of the disease and ways to treat it.
A popular area of research has been looking to develop a biomarker. According to Rylett, this could potentially take the form of a blood test or imaging test.
“The idea is these biomarkers would be predictive of who is at highest risk of developing Alzheimer's or other dementias at some point in their lives,” says Rylett.
“If we knew that first, then we could start looking at other drug and lifestyle choices that could impact the course or trajectory of the disease.”
Straight talk on health, illness and recovery. Get better.