A Tangled Mystery

Scientists are trying to make sense of the processes that lead to Alzheimer’s disease



The microscopic changes in the brain that are thought to lead to Alzheimer’s disease can be tough to understand. The prime suspects are clumps, or amyloid plaques, of a protein called beta amyloid found in the spaces between brain cells, and tangles of another protein called tau found within damaged brain cells. 

Physicians began describing these plaques and tangles, often referred to as neurofibrillary tangles, more than a century ago after Alois Alzheimer used microscopes to examine the brains of people who had died from what we now call Alzheimer’s disease. The presence of large numbers of these plaques and tangles on microscopic examination of the brain after death in someone with dementia indicates the cause was Alzheimer’s disease. 

These changes first appear at the bottom of the brain, in areas important for memory and learning, before spreading into other parts of the brain, says Dr. David B. Hogan, a specialist in geriatric medicine at the University of Calgary.

“If you examine the brain of someone with Alzheimer’s disease under a microscope, you will see an abnormal number of amyloid plaques—that look like dirty smudges—between brain cells.

Within them are neuro-fibrillary tangles that really look like twisted strands of hair, which are made up of an abnormal form of the tau protein,” he says. 

The plaques and tangles develop over years. They are thought to disrupt the normal function of brain cells, leading to their death, and stir up inflammation.

The damage, and the eventual death of brain cells in particular parts of the brain, are believed to lead to the thinking changes, self-care deficits and other behavioural symptoms of Alzheimer’s disease.

Early on, those affected are likely to be able to cope with some damage to their brains, but once it reaches a certain threshold, the brain’s ability to rewire itself and deal with these changes is overwhelmed. 

Though there’s plenty of scientific evidence supporting the belief that amyloid plaques and neurofibrillary tangles cause Alzheimer’s, this hasn’t yet been proven conclusively. More research is required on the cause of Alzheimer’s disease and other dementias so they can be more effectively treated and prevented.

“At this time, we don’t fully understand what’s going on in the brain of someone with Alzheimer’s disease,” Hogan says. 

Much money has been spent on developing drugs to prevent the accumulation of these proteins or to stimulate their removal from the brain. But unfortunately, none of these treatments has been shown to be effective, making researchers continue to wonder if they truly understand this condition.

Hogan says one theory about why the drugs developed to deal with these abnormal proteins haven’t worked is they may have been started too late. Possibly, treating people earlier, when the brain changes are less extensive and the person has minimal or no symptoms, would yield different results, but that has so far not been proven.

Many people live long lives with no significant cognitive problems, yet on autopsy their brains will show tangles and plaques, though usually not as widely distributed as what you’d see in someone suffering from Alzheimer’s disease.

“Certain types of brain scans and other investigations like a spinal tap might be able to detect early evidence that more-than-normal amounts of these proteins are in a person’s brain,” Hogan says.

“These investigations might be useful in research studies, as they could be used to choose people who are at a higher risk of Alzheimer’s disease for studies of drugs and lifestyle changes to prevent this condition,” he says.

But, he warns, these tests at the moment are of uncertain value, and not recommended for everyday use.

“We don’t fully understand what the results mean for the person, or what we should—let alone can—do about them.”  [ ]