Observing Brain Synapses
Relating Alzheimer's Symptoms to Synapses
Summary
In the last post, I described how synapses, the connections between neurons in the brain, might be involved in storing memories. You may have wondered if it is possible to observe a relationship between synapse changes in the brain and dementias like Alzheimer’s. In this post, I explore experiments that do this.
Synapse Theory and Alzheimer’s Disease
Back in the 1980s, several scientists used the electron microscope to count how many synapses there were in specific areas of brain tissue. They reported that the number of synapses declined with advancing Alzheimer’s disease symptoms.
It is tempting to conclude that this means that synapse loss causes Alzheimer’s disease. It may not be that simple.
Electron microscopes are powerful devices that can reveal features as small as about 50 billionths of a meter, far smaller than the width of a human hair. Brain synapses have a diameter much larger than this, so an electron microscope can see synapses.
These studies used both biopsied and postmortem tissue — the biopsies coming from tissue removed during brain surgeries for various conditions. The biopsies raise the question of whether synapse loss was due to Alzheimer’s or the condition. Postmortem tissue does not pinpoint when the synapse loss occurred. Finally, since there were limited brain locations observed, it was possible that the synapse loss was not widespread in the brain. Even so, these studies were important beginnings.
More Advanced Techniques
In recent years, an imaging device called a PET scanner was used to make more sophisticated synapse observations. A radioactive molecule was injected into living human subjects that attached to a protein found in synapses. The resultant radiation revealed synapse locations — eliminating the need for invasive biopsies. Images constructed from this data provided a quantitative measure of where synapse loss occurred throughout the brain. These studies were a major improvement on the earlier work, and showed widespread synapse loss was related to Alzheimer’s cognitive decline.
Finding Meaning in Mechanism
You may have read a mystery novel where the evidence is consistent with many theories of the crime, pointing to more than one suspect. The police construct a compelling case against one suspect, but a private detective proves that someone else did it.
Biology is far more complicated than a murder case. Both the electron microscope experiments and the sophisticated PET scans were compelling because they were associated with the progression of the disease. However, they do not reveal the mechanisms of why or how synapses disappeared because they were not designed to do that.
While the synaptic loss might account for the disease symptoms, something else not measured might also be important. As I explore this mystery in subsequent posts, I will look for research that reveals mechanism . . . if it is there.