What you see in the header image of The Naive Observer is part of a dendrite. Dendrites are the information collecting arms of neurons. Neurons also put out another long, snaking and highly branched arm called an axon, which carries info by conducting tiny electrical pulses away from its cell body. Axons transfer those pulses to dendrites at small connections called synapses. On the dendrite in the header, each little protrusion is the dendritic counterpart of a synapse, called a spine. This is where messages are received. In this picture, a fluorescent protein makes only the dendrite glow, so you have to imagine all the axons contacting each spine. They are there, you just can’t see them.
Synapses are where the action happens in the brain. Our brains (and by extension, we) are so complex and able to do so much because of the info that passes between neurons at synaptic connections. When it comes to it, we are our synapses and the electrochemical signals that pass through them. So each little spine on the header dendrite could be a part of a memory, an ability, something totally subconscious that we would never be aware of or any of myriad other brain functions. Regardless of what a specific spine does though, this is what part of the experience of a living being looks like in the flesh.
Knowing this, it should come as no surprise that losing spines results in major changes to a person’s mental make up. This is exactly what happens in Alzheimer’s disease; along with a host of other structural changes in the brain, dendritic spines disappear, and with them likely go parts of the person suffering the disease. However, it is hard to study the loss of spines over time in human’s with Alzheimer’s, so efforts have been mounted to produce mice that are genetically engineered to develop Alzheimer’s. To understand these mouse models, you should know 3 main cellular alterations that cause and accompany the disease:
1.) A protein called Amyloid β accumulates in plaques and “fibrillary tangles” around neurons and cerebral blood vessels.
2.) Certain neuronal subpopulations die off.
3.) Many synapses disappear at an early clinical stage of the disease. Since synapses are thought to be the cellular basis of memory, loss of synapses (and thus spines) is expected given the well known memory deficits involved in Alzheimer’s.
Mouse models of Alzheimer’s are based on the first point. To generate these models, people have genetically engineered mice with mutated amyloid β (Aβ) genes that result in the protein eventually accumulating, aggregating, and forming plaques. It was originally assumed that the Aβ plaques were the major problem in Alzheimer’s although no one is sure whether these plaques are actually the pathological agent, just a result of something else that is really causing the disease, or if the formation of the formation of these plaques are actually a cellular response to try and counter the disease. However, while we still aren’t sure about the plaques themselves, it’s becoming increasingly clear that soluble Aβ particles that exist before plaques form are also extremely detrimental. In fact this became clear when people started studying the mouse models that had the mutant Aβ: these mice started presenting cognitive deficits (like poor performance on memory tasks) before the plaques even formed.
In a paper published this March, Perez-Cruz and friends took 2 of these mouse models and examined the cellular architecture of neurons in a part of the brain called the hippocampus – famous for its role in learning and memory. Both of these types of mutant mice have mutations that lead to increased expression of Aβ protein, leading to Alzheimer’s-like symptoms in the mice. These mutations were actually first found in human families affected by congenital, early-onset Alzheimer’s. One of these families is Swedish, and the other is from London, so the mutations were aptly named the Swedish and London mutations.
Perez-Cruz and friends used these mice to essentially reproduce previous findings, but did it in such a way as to synthesize some new information. They showed that both of these mutations lead to decreased spine density, and that this is presumably the cause of the memory deficits that the mutant mice present. However, by assessing the levels of neural activity in the the hippocampi of these mice, they provide evidence that the spine loss is a result of unhealthily high levels of activity. They go a step further and show that these high activity levels may be a due to a decreased number of inhibitory neurons that normally help to keep activity levels at more acceptable levels. Thus, in their conclusion, Perez-Cruz and friends offer that perhaps by finding a way to keep these inhibitory interneurons healthy we could help prevent the spine loss associated with memory deficits in Alzheimer’s.
How to target specific populations of inhibitory neurons healthy is a big task though – most importantly we have to figure out what is causing them to be sick? The plaques or something completely different? While that is hopefully being pursued, Alzheimer’s is a huge field of study right now, with lots of work going into understanding the disease pathology and producing effective treatments. However, with Alzheimer’s rates rising in an aging population, help can’t come soon enough, so we’ll have to keep our finger’s crossed for now.
If you’d like a more positive conclusion, you can have a look at this – I’ve heard a couple of talks in the past couple months that tell me art therapy is extremely useful in alleviating the isolation of a deteriorating brain.
Click here for an In Depth look at the Perez-Cruz and friends’ paper.