So we're going to talk about disease in movement and movement disorders. Many of these diseases are in the category of neuraodegeneration. Not all of them, but a big chunk of that is in neuraodegeneration. So I decided to pick those areas in neurodegeneration as an example to present what do we understand? How do we understand the process? So I picked one disease to start with on purpose. And that is a disease you have known quite a bit about, which is Alzheimer's disease. Alzheimer's disease has about 20% overlap with Parkinson's disease. That's not a small number, okay. Although Alzheimer's disease is not a typical movement disorder, but it has a strong component of it. And the reason I picked that disease is exactly because you had previous knowledge about it from other lecturers from your previous studies. So if we want to understand a disease, we usually look at several factors. In that disease, Alzheimer's disease, Parkinson's disease, so on and so forth, there's always a question of genetic factors versus environmental factors. The old question of nature and nurture, okay. So there are genetic factors, for sure, and there are environmental factors in these disease developments. A second very, very obvious feature is that there are multiple cellular/molecular defects or pathways involved in these diseases. I ask you to simply, randomly flip to any sections, and you will find, well, this one is involved or that one is involved. As a matter of fact, it's hard to find any process that is not involved in a disease. The third one is almost all of those diseases may have a stage or age dependence. This means at a young age, they're probably okay, and then when people grow older and older, then they have a pathology gradually manifesting itself. This is true for Alzheimer's disease, for Parkinson's disease and for many of these neuraodegenerative diseases. The last one I want to make is it's always true that these diseases manifest them with many pathologic factors. But pathologic ones, many of them are not pathogenic ones. So these words are very similar to each other, but I want you to pay attention to them. Pathologic means anything that’s associated with the disease, but pathogenic means the change of that actually is a causal event to later development. So pathogenic is a lot more stringent, okay. And these are the features, recurrent features, in neurodegeneration. So I picked four diseases to mention to you. We'll focus on three of them in class discussion, and leave one of them to you to just practice the way to understand or to know about a disease. These four diseases are Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and ALS. If you do a PubMed search of neurodegeneration, these are the four diseases that came up as the four top ones that have the most papers published. Alzheimer's disease is the single, one biggest neurological disease ever, it's the biggest one. Parkinson's is the second. The other two, however, are not, quote, unquote, big diseases. If you look at the patients population, it's not that high. However, in this study those, especially HD, contributed in almost every critical move in our understanding of diseases or the way we can study diseases. So I picked that one. And out of that four, number two, three and four are typical movement disorders. The first one, as I mentioned, is not usually considered as a movement disorder, but has a very strong over-lapping component with movement disorders. So I'll start with Alzheimer's disease that you are actually quite familiar with. Now, all these diseases, three typical movement disorders in a one or a half, what do we know about them? We know that there is always neuronal loss in a particular brain area. In Alzheimer's disease, it's a diffused neurodegeneration, starting from temporal cortex, hippocampus and gradually it spreads. In Parkinson's disease, it's the degeneration of dopaminergic neurons, mainly in substantial nigra. In Huntington's disease, the degeneration occurs in caudate nucleus, in striata. It's a very specific type of neuron called median spiny neuron that are dead in this disease. In ALS, of course, it's the motor neurons that are dead in this disease. So they have different, specific, neuronal cell death.