The underlying causes of the memory loss, confusion and disorientation of Alzheimer’s disease (AD) are complex, but not altogether unknown. This post describes the physical changes in the brain that underlie and contribute to the dementia of AD. Those changes occur in both the appearance and the connections of brain neurons. (To read about normal brain, for comparison, click here.)
Normally, long threadlike structures called neurites extend from neuronal cell bodies and connect neuron to neuron in an organized pattern.
Looking through the microscope at an Alzheimer’s brain, researchers see that this pattern has been disrupted. In some areas, neurons have died and disappeared, leaving fewer cells available to carry information.
There are some neurons whose cell bodies are filled with twisted fibers—as if their neurites had become ingrown. Neurons filled with fibers like this are called tangles. They are the dark blue, spider-like objects in the picture above. Often, the neurites that reach out from these cells are abnormally short or are missing altogether. A few of the tangles, called ghosts, are already dead; their outside cell walls have disintegrated. The twisted clumps of fibers are all that remain.
Many neurons in AD brain have normal-looking cell bodies, but their neurites curl about in a random pattern, not making proper connections. Still other neurons have neurites that have become embedded in abnormal clumps of protein found outside the cells, instead of making normal connections with thier neighbors.
The abnormal clumps of protein found outside of cells are called amyloid plaques. These are the large, diffuse circular structures in the picture above. They are medium blue in color and are larger than the dark, spider-like tangles. A small number of such plaques are found in the brains of healthy elderly individuals. However, individuals who have Alzheimer’s disease have many, many more of them–particularly in the areas of the brain involved with learning and memory.
The plaques contain a protein called beta-amyloid (or A-beta). In advanced cases of AD, beta-amyloid is also deposited in and around the blood vessels of the brain. That deposition is called cerebrovascular amyloidosis, or CVA.
Together, plaques and tangles interfere with the normal connections of brain neurons and contribute to the death of neurons in the AD brain.
Plaques and tangles, along with CVA and diffuse cell loss, are hallmarks of Alzheimer’s disease, and are easily observed in AD brain tissue. But they don’t even begin to tell the whole story. There are many other changes that occur in the AD brain and cause it to lose function. More on those next time.
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