So today, we'll talk about some disease and we try to understand physiological processes through diseases. And the first disease we're going to talk about is Alzheimer's disease. There are several diseases in the nervous system that associated with protein aggregation, mislocation of these proteins and the B aggregates formed inside of the cell. So these diseases include Alzheimer's disease and Parkinson's disease. So in Alzheimer's disease inside of the neuron, we have aggregates formed with hyperphosphorylated tau protein. The black staining labeled here. And if we take a close look of these aggregates, we'll see these parallel the filament inside of the cellular structure. So we call it a paired helical filaments inside of the cell. And in Alzheimer's disease, we have another kind of cellular aggregates formed outside of the cell extracellularly. And it formed it with amyloid beta peptide made of these amyloid plaques or senile plaque. In the Parkinson's disease we have also a structure called a Lewy body inside of a cell, is aggregates formed with alpha-synuclein. It's a study of disease is a way to understand a normal process or normal physiology. The dementia, Alzheimer's disease is the most common form of dementia. Dementia is a group of brain cells that die eventually and that will lead to loss of memory and mental function. Besides Alzheimer's disease, we also have some other types of dementia. For example, vascular dementia. It's related to lack of blood flow of certain brain areas, induces the neuronal cell deaths in that particular brain area. So in Alzheimer's disease and vascular dementia, sometimes they can happen together in some brain area, so we call it mixed dementia. So mixed Alzheimer AD type of dementia and vascular dementia. And other causes of dementia include frontotemporal dementia and dementia with fluid body that often happen in the late stage of Parkinson's disease and CJD caused by infection of a prion particle. Alzheimer's disease is named after Dr. Alzheimer, and this is Dr. Alzheimer and this is the patient he first describe that has this kind of dementia. So Alzheimer's diseases is a progressive brain disorder, gradually destroy a person's memory and ability to learn, to reason, to make judgment, communicate and carry out daily activity. In the late stage of Alzheimer's disease, people can have some personality change and some behavioral a symptom like anxiety, suspiciousness and delusion a hallucination. So if we compare the brain of Alzheimer's disease patient to the age matched control, we'll see dramatic shrinking of the volume of the brain. So that suggest massive cell loss happened in Alzheimer brain. So the progression of this disease, it can last pretty long. Sometimes it can last for 20 years and then the area controlling memory, learning and the memory get destroyed, get affected first. And then it's a gradually, it progressively affects the brain area close to that area. So if we look at this picture, so entorhinal cortex and hippocampus are first of two brain area that affect it in AD, Alzheimer's disease. The light blue region here, and then because it is a kind of neurodegenerative disease. So that means a group of neuron die and in the other group of neuron that have the synaptic connection with this group of neuron die after. And in just like the best signal spread to the brain area close by. So the brain area close by the neuron in those area die. And then eventually, in advanced stage, the late stage of the disease, loss of the gray area can be affected, including the frontal lobe and sometimes can be the visual cortex. So what is the cause of disease? We still don't know what is exactly cause of disease. We see some symptom, we see some pathological markers of this disease. One is called plaque and then the other one is called tangle. The plaque is made of amyloid peptide and it's extra celluraly. And a tangle is intra cellularly and is made with hyperphosphorylated tau protein. So whether these pathological hallmarks are a cause of the disease or just simple consequence of the disease, we still don't know. So in this picture, inside of the cell, inside of the neuron, we have neurofibrillary tangle made of tau protein. And then outside of the cell we have senile plaque, made up of amyloid peptide and this two thing can induced neuronal cells death. There are several risk factors for this disease. One of course is age. So the incidence of this disease at age over 65 is around 5%. If the age is over 85, the risk reaches to near 50%, so nearly one in two elderly over 85 will have Alzheimer's disease. Family history of the genetics, we do have some some families or some patients that carry familial mutations of this disease. And the paths to prevention, we don't have effective prevention now because we don't understand how this disease happens. So we don't have a clear target for therapy or for parentia. So all this data sometimes comes from statistics, sometimes are quite controversial. So gene environment, so which one contribute to the disease more? We still don't know. There are in the whole disease population, we have around 5% that carry familial AD mutations and the other 95% are sporadic, meaning there is no clear genetic mutations in those 95% patient. Head injury, if you have trauma or head injury, your risk of having Alzheimer's disease increases. And in head and heart connections, if you have a disease in the vascular system that you risk of having Alzheimer's disease increase. There are some misunderstanding of this disease. One is the memory loss is a natural part of aging. As you age, as you getting older your memory will get worse and worse. Well that's kind of true, but does not totally true there's distinct differences between Alzheimer's, dementia and age related memory change. I listed the comparison of the two here. So for the Alzheimer's disease the forgetting can be the entire experience and for age related memory decline it's just part of an experience it cannot be the whole event as a whole. For Alzheimer's disease, if your forget it's rarely that you can remember later. But for age related memory decline, sometimes you can still recall the event later, and there's another misunderstanding that this disease is not fatal. While it is true, it doesn't kill the patient by itself, but sometimes it can lead to some accidents of the patients. For example, in the late stages of the Alzheimer's disease people cannot memorize the details or cannot memorize common sense of life. He may not remember that fire can be harmful and then he can touch the fire by the hand, just by hand and that's an accident. And it happened to her and an Alzheimer's disease patient can go out on the street and easily get lost on the street. So this disease can easily cause all kinds of accident that will sometimes be fatal. And then the link, where of sot of association between aluminum and Alzheimer disease is negative. Well the rumor of aluminum, the correlation of aluminum and Alzheimer's disease came from a study with a small group of person. And then one pupil repeated that experiment with large population, with large sample size. And then the date or the results are not repeatable. For Alzheimer's disease per se The amount of the level of aluminum doesn't correlate with the instances of the disease, but intaking too much aluminum is not good for health. So another needs understanding is that there are several things available to stop this disease, but as we just mentioned because we don't understand the pathological process of this disease. We don't know how the neurons die in this disease. So there is no effective drugs we can use. There are some drugs that are approved by FDA that can improve the symptoms, and that includes cholinesterase inhibitors. Because in the disease, in early stages of this disease, loss of the nueronal cells that has happened in cholinergic neurons in hippocampus. So the cholinesterase is an enzyme that can kill the astocoline. So use the inhibitor to this enzyme can kind of improve the symptom. Memantine is an antagonist to an MDA receptor, and the effect of this drug is general. It's not specific to AD itself. Too much neuronal excitation can induce glutamate toxicity. So memantine simply decreased chance of having this glutamate toxicity. Vitamin E is another general drug is not only specific to AD as well. It is an oxidant, and it increase the general health of the brain.
