New Understanding of Alzheimer's Disease:
Many Lessons Learned Through Autopsy

As a result of Alzheimer's disease, there are basic structural changes in the brain that are visible both on inspection and by microscope. On inspection, one can see an increase in the size of the fluid-filled cavities in the brain, which are called the cerebral ventricles. Also, the grooves on the surface of the brain become enlarged because of fluid accumulation. By microscope, one can see other changes, the most striking of which, in Alzheimer's, are the so-called plaques and tangles. The tangles are structures present inside the cells of the brain. The plaques are protein-like substances found near the brain cells. The question for scientists has been, what is the relationship between these brain changes and the many memory and functional losses that occur in Alzheimer's disease?

Research at the NYU Alzheimer’s Disease Center has uncovered many of these relationships and has resulted in a greatly improved understanding of the nature of Alzheimer's disease.

In 1979, our researchers showed that the increase of fluid in the brain, both on the surface and within, is strongly related to memory loss and other forms of thinking capacity in Alzheimer's disease.

In our more recent work, using materials obtained from autopsy, we have uncovered many important relationships between brain changes and the deterioration of cognition and functional in Alzheimer's disease.

In the 1980s, we found that we could identify many important functional losses in patients whose dementia was so severe that they were thought to be untestable. This severe portion of Alzheimer's disease encompassed about half the duration of the disease.

In our autopsy work we learned that these functional losses are accompanied by striking changes in a sea horse- shaped part of the brain known as the hippocampus, the Latin word for seahorse.

We found that the decrease in size of the hippocampus was related to the progressive functional losses in Alzheimer's disease. Volume loss was accompanied by loss of brain cells. Brain cell losses in some regions of the hippocampus were particularly striking and more severe than in others.

Further study indicated that, in regions of the hippocampus where there were brain cell losses, there were also progressive increases in tangle formation in the cells. In contrast to the tangles, the number of plaques did not relate to the functional, cognitive, cellular losses, or the decrease in brain volume. These observations have resulted in a fundamental increase in the understanding of the basic nature of Alzheimer's disease.

We now know that Alzheimer's disease causes continuous brain changes over a period of approximately 20 to 25 years. However, some brain areas are much more affected than others, and studies made possible through autopsy have shed some light on the reason.

The brain has cells that are similar in many ways to electrical generators. These cells have axons that function like wires coming out of an electrical generator and communicating with other cells. The axons are covered with myelin, a fatty substance that is similar to rubber insulation on a wire. Just as rubber protects the wire, the myelin protects the axons and ultimately the neurons.

Through the study of material only obtainable by autopsy, we now understand that myelin appears to be vulnerable to the Alzheimer's disease process. It is the destruction of the myelin that seems to account for the increase in fluid in the brain, which we first discovered more than 20 years ago. These findings made possible by our autopsy program are now pointing researchers in the direction of potentially effective treatments for Alzheimer's disease.