How does Alzheimer’s wreak so much havoc in the brain?


My grandmother has Alzheimer’s disease. Over the past few years I have watched the disease take a toll on her judgment, memory, even her personality. How does Alzheimer’s wreak so much havoc in the brain?


In the past 25 years, medical science has learned a great deal about what causes Alzheimer’s disease. Before that, we basically knew just that the brains of people with this disease, viewed with a microscope, had some unusual features. We knew that the disease caused brain cells to die prematurely, but we didn’t know why. Today, I think we are closing in on understanding some major causes (if not all of the causes) of brain cell death.

Early on, Alzheimer’s disease affects the brain’s limbic system and cerebral neocortex. The limbic system is central to memory and learning. It also links emotions and behavior. It is the line between what we want to do and what we actually do. The cerebral neocortex controls conscious thought. Damage to this area leads to problems with language, math and reasoning.

Ongoing communication between the limbic system and neocortex links thinking and emotions. The back-and-forth between memory and emotion, thought and action, is the foundation of personality. That’s why damage to these two areas is so devastating.

Other parts of the brain are not affected until later in the disease. Examples include the brainstem and cerebellum, which control basic functions needed for survival. When these brain areas are affected, swallowing, walking and coordination become impaired.

Twenty-five years ago, we knew that the brain cells that do the thinking — neurons — communicate with one another using chemicals called neurotransmitters. As Alzheimer’s disease takes hold, levels of one neurotransmitter, called acetylcholine, drop sharply. Without enough acetylcholine, different areas of the brain cannot communicate normally with one another.

We also knew that there were two unusual microscopic structures in the brains of people with Alzheimer’s, called plaques and tangles. We knew that plaques contained a chemical called amyloid beta, and that tangles contained a chemical called tau. (I’ve put an illustration showing the plaques and tangles of Alzheimer’s disease, below.)

Plaques and tangles


The brains of people with Alzheimer’s contain neurofibrillary tangles inside neurons and amyloid plaques between neurons.


Finally, we knew that areas of the brain with lots of plaques and tangles were most likely to have dead neurons. In advanced Alzheimer’s, the loss of neurons is so dramatic that the brain actually shrinks. So there was circumstantial evidence, but no proof, that amyloid beta and tau might be important causes of the death of neurons.

In the past 25 years, scientists have obtained strong evidence that amyloid beta and tau really are important causes of the death of brain cells. And scientists have discovered several other brain molecules that are also important. I predict you’ll be hearing more about apolipoprotein e4 (ApoE4) and a gene regulator called REST (you don’t want to know the full scientific name).

If these molecules are all important in causing Alzheimer’s disease, then targeting them with new drugs may someday prevent and even reverse the disease.