RESEARCH INTO STRUCTURAL CHANGES INSIDE THE BRAIN IN CASE OF ALZHEIMER’S DISEASE
Some of the earliest research into Alzheimer’s disease involved examining the structural abnormalities that occurred in the brain and which were visible through a microscope. As more powerful equipment such as the electron microscope became available, the most detailed structural changes within the cells themselves came under scrutiny. Our research into the structural abnormalities has now proceeded even as far as examining the molecular structure of neurofibrillary tangles and some of the components of the senile plaques. Although in itself not directly leading to new treatments, this approach has certainly pointed us in the direction of further avenues of research that have yielded important results. In addition, this knowledge has increased our understanding of some of the processes that actually go wrong, and how and why this might happen.
Outside the Brain
As well as revealing abnormalities in the nerve cells themselves and also their fibres, we have discovered that there are changes, including the formation of neurofibrillary tangles, in at least one structure outside the brain itself. The nerve fibres associated with our sense of smell pass from the nose through small holes in the skull to a pair of structures, one on each side, about the size of a grain of wheat. These are known as the olfactory bulbs and are connected to the brain. Those parts of the brain that are important for appreciating and distinguishing between different smells are very heavily afflicted with neurofibrillary tangles and we now know that the olfactory bulbs are similarly affected.
In addition, it has recently been shown that the nerve fibres in part of the lining of the nose are also abnormal. Although this finding may well turn out to be a red herring, it could indicate one route of entry into the brain of a toxic substance or infectious agent such as a virus. It would be relatively easy for some viruses that live in the nose to pass into the brain along this pathway and then to spread to different parts of the brain.
Detailed study of the neurofibrillary tangle has shown that it is made up of sub-units arranged in a spiral fashion. There is a debate in progress about the possibility that the structures may be abnormal forms of a protein that is usually present within nerve cells, and which may be part of the nerve cells’ normal internal skeleton or of the system of tubules that nerve cells use to pass substances from one end of nerve fibres to the other. As the tangles grow, they probably disrupt the normal transport processes that take place within the cells.
A similarly detailed study of the structure and arrangement of the senile plaques has revealed that many of them are formed in close association with minute blood capillaries. This has raised the possibility that an as yet unidentified substance may leak out of the blood vessel into the brain where it causes damage, leading to the formation of senile plaques and perhaps also, albeit indirectly, resulting in the formation of neurofibrillary tangles in some neurones. Study of the arrangement of neurofibrillary tangles in different parts of the cortex and elsewhere in the brain has indicated that it may only be certain groups of nerve cells, those whose fibres link up with each other, that are affected. Other nerve cells, whose fibres make different linkages, appear to be unaffected. This could be taken to imply that an infectious agent or a toxic substance is being passed from nerve cell to nerve cell, causing the formation of neurofibrillary tangles and other damage along its route. More research is needed to decide whether this is true.
Enormous strides have been made in the last ten to fifteen years in our understanding of the changes in the brain, and outside it, in Alzheimer’s disease and some of the other dementias. This information has been very helpful in the search for underlying causes and in the attempts to develop more effective treatments. I firmly believe that we are presently at the most important and exciting phase of the drive to conquer Alzheimer’s disease. We should look forward to the future with confidence and hope.
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