Biological basis of alzheimer's disease

in this video I'm going to talk about the biological basis of Alzheimer's disease Alzheimer's and there's disagreement whether to use the apostrophe s whether to call it Alzheimer's or just Alzheimer disease I'm a little bit more used to this so I'll use this Alzheimer's disease is the most common disorder in the category of disorders called the dementia dementia or with newer terminology called the neurocognitive disorders what these disorders involve is a loss of cognitive functions cognition cognition is kind of the thinking functions of the brain and Alzheimer's disease in particular usually starts with a decreased ability to form new memories so the main early complaint is memory troubles with Alzheimer's disease and then those memory troubles progressively worsen and later other cognitive functions usually progressively deteriorate as well other people start to notice that the patient gets confused or disoriented there may be episodes of getting lost and having progressive difficulty with things like work driving shopping cooking or managing finances as the disease progresses in addition to cognitive abnormalities emotional and behavioral abnormalities also often occur but other nervous system functions like basic motor and sensory functions are usually spared through most of the course of the disease at later stages when Alzheimer's disease becomes most severe patients lose the ability to perform what are called basic activities of daily living I'll just write a DL for short but these basic activities of daily living include things like toileting bathing dressing or eating in these patients will eventually require full-time nursing care to attend all of their bodily needs because they won't be able to take care of those things themselves this is a famous image when talking about Alzheimer's disease because this was the first patient that was described with Alzheimer's disease this person was studied by dr. Alzheimer and that's why the disease is known by that named as of 2014 when I'm making this video our understanding of the cause of the disease is very limited to show you some of the things that can be seen abnormal with the brain with Alzheimer's disease I have a few illustrations of the brain here we're looking at the brain from the left side here we're looking at up at it from the bottom from underneath and then here are a few illustrations showing the brain as if it's been cut just like this and we're looking at the inside of the brain tissue and the layer of tissue on the outside and when we compare brains from people without Alzheimer's disease and people with Alzheimer's disease the really obvious finding when looking with the naked eye is that the brain tissue has decreased in size so you can see that this this brain is kind of shriveled up and wasted away compared to this brain without Alzheimer's disease the medical term for a decrease in size like this is atrophy let me just write that word down atrophy and all this word atrophy means is that the bulk of a kind of tissue is decreased it's decreased in size and with Alzheimer's disease it's the cerebrum this topmost part that's colored in these different colors here that often dramatically decreases in size the severity of the atrophy often correlates with the severity of the dementia so the patients with really severe cognitive deficits often also have dramatic shrinking of the volume of the tissue of the cerebrum like they're showing in this illustration here this atrophy usually starts in part of the cortex which is the layer on the outside of the cerebrum and it particularly tends to start in what are called the temporal lobes these are the temporal lobes if we're looking up at the brain from underneath let me just write that temporal lobes temporal lobes and here in this illustration they've shown this as well they're showing a normal brain with normal amount of brain tissue and next to it they're showing a typical brain for a person with severe Alzheimer's disease where the overall brain tissue is decreased and in particular these areas of the temporal lobe these kind of inside parts of the temporal lobe and these parts we know are particularly important for forming new memories so these parts tend to atrophy first which goes along with the early clinical abnormalities of Alzheimer's disease of having trouble forming new memories later atrophy develops in many cortical areas of the temporal lobe the parietal lobe and the frontal lobes so widespread cortical areas of the cerebrum develop atrophy as the disease progresses and these other areas that atrophy we know are important for many of the other cognitive functions that are typically affected by the disease under the microscope like in this actual photograph here taken with a microscope of some of the cerebral cortex hi murmurs disease there are three main abnormalities that can be seen with typical microscope studies the first is that we can see loss of neurons so neurons are clearly lost from the brain tissue in these areas of cerebral cortex that are actually decreasing in size to the naked eye as well so people go through microscope slides of these areas of cerebral cortex and count up the neurons they'll see a decreased number of neurons these sorts of cells right here are neurons within the rest of the brain tissue surrounding them the second abnormality are called plaques plaques and these are some of the types of plaques that can be seen these are also called amyloid plaques because they're made up of a protein called beta amyloid primarily these amyloid plaques occur in the spaces between cells so they're outside of the neurons of the brain in the space between them and there are these abnormal clumps of this beta amyloid protein the third typical finding are called tangles tangles or neurofibrillary tangles and I don't think we can see that at this magnification but if we look to with a higher magnification at some of these kind of sicker looking neurons like maybe these guys within them we would probably see these neurofibrillary tangles which are abnormal clumps of a different protein called tau and these neurofibrillary tangles are located inside neurons so the amyloid plaques are in the space but clean cells in the neurofibrillary tangles made up of these abnormal clumps of tau protein are inside of neurons both of these abnormalities develop from proteins that are normally present in the brain beta amyloid and tau but for reasons that are not yet fully clear these proteins are changed in some way that's abnormal that causes them to clump together and form these amyloid plaques and neurofibrillary tangles here an artist has drawn something going abnormal with processing of this beta amyloid protein that leads to them clumping together to form these amyloid plaques and here an artist is trying to show these neurofibrillary tangles inside of diseased neurons and how this tau protein can abnormally clump together inside the neuron to form these pero February tangles so we can see these things on microscope slides of brain tissue affected by Alzheimer's disease but it's actually not totally clear yet if the problem is that these things form and that kills the neurons in the brain causing the loss of neurons or if these things are just a byproduct of some other process that's causing the loss of the neurons so that even if we fix these problems of the amyloid plaques and the neurofibrillary tangles it's not yet totally clear if that would prevent the neurons from being lost in the brain a particular group of neurons at the base of the cerebrum around here called the base Salas nucleus base Salas or it has a longer name of the nucleus base Salas of Manor the neurons in this nucleus this group of neurons is often lost early in the course of Alzheimer's disease these neurons appear to be important for cognitive functions these neurons send long axons to many areas of cerebral cortex throughout the cerebrum and what they do is release the neurotransmitter called acetylcholine acetyl choline and loss of this diffuse projection of acetylcholine from the base Allis nucleus to the cerebral cortex appears to contribute to the cognitive dysfunction of the disease because certain medications that affect this neurotransmitter system often improve some of the symptoms of Alzheimer's disease one of the very interesting findings in people studying Alzheimer's disease is that long before cerebral atrophy or the microscopic abnormalities develop and years or even decades before cognitive loss occurs there appears to be abnormalities of energy use and abnormalities of many of the molecules related to energy pathways inside brain cells there's evidence that the metabolism of the primary fuel source of brain cells which is called glucose and the function of mitochondria which are organelles that are a primary site for energy metabolism both appear to be abnormal long before the other abnormalities appear also there have been some findings regarding the effects of cellular energy use which are called oxidative stress which appears to be increased and oxidative stress is known to be a potential source of damage to brain cells but so far the cause of these changes is unclear another very early finding is that synapses the place where neurons contact and communicate with each other appear to not function normally long before the other abnormalities are seen and the cause of this is also unclear many things have been associated with the risk of developing Alzheimer's disease which may play some role in causing the disease at least in some people these include multiple genetic mutations many of which involve processing of the protein beta amyloid the primary component of amyloid plaques there's also another gene called a pony for a pony for that's strongly associated with the risk of developing Alzheimer's disease but it's involved in metabolism of fats in the body so it's unclear how it's related as well and then there are very separate things like medical conditions that cause dysfunction of blood vessels such as high blood pressure appear to increase the risk of the disorder as well and then on the other hand certain things appear to decrease the risk of developing the disease or at least seem to delay its onset than some people and these include having greater amounts of education and working at cognitively challenging jobs that involve lots of difficult thinking but how all these different things could interact to affect the cause or course of Alzheimer's disease is still very unclear


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