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Amnesia, dissociative disorders and delirium: Pathology review
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Pick disease p. 730
Frontotemporal dementia, or FTD for short, refers to a degeneration of the frontal and temporal lobes of the brain. FTD is often mistakenly called Pick disease, or Pick’s disease. However, this is only a specific subtype of frontotemporal dementia, characterized by the presence of Pick bodies, which are tangles of abnormal nerve cell proteins called tau proteins.
Now, if we take a step back and take a look at the brain - it can be divided into four lobes: the frontal, temporal, parietal, and occipital lobes. Within each lobe is a dense network of neurons, which allows neurons to communicate with one another. Like most cells, neurons have a cytoskeleton made up of filaments and microtubules that give the cell its structure. Microtubules help neurons move molecules along the length of the cell, kind of like a railway track. And just like in a railway track, the individual units of a microtubule, called tubulins are tied together with a protein called tau. Tau comes in six different shapes and sizes, or isoforms, and one of the key features of these isoforms is how many times a particular sequence of 29 amino acids gets repeated. For three of those isoforms, it's repeated three times -- they're called the 3R isoforms -- and for the other three, it's repeated four times -- they're called the 4R isoforms.
Although it's not completely understood why, in frontotemporal dementia, abnormal protein inclusions form in the cytoplasm or nuclei of neurons. These inclusions are often made up of tau proteins. Specifically, in the case of Pick disease, 3R isoforms of the tau protein get hyperphosphorylated, meaning that phosphate groups keep binding onto the proteins until no more will fit. These hyperphosphorylated tau proteins change shape and stop being able to tie together the tubulins in the neuron's cytoskeleton. What's more, the hyperphosphorylated tau proteins start clumping together, forming tangles of tau protein. This makes Pick disease what's called a tauopathy, just like Alzheimer’s disease. A key difference is that the tangles in Pick disease, are called Pick bodies, and they’re only made up of the 3R tau isoforms, whereas the tangles in Alzheimer’s disease, are called neurofibrillary tangles, and are made up of both 3R and 4R tau isoforms. In other cases, intracellular inclusions are made up of a protein called TDP-43, which is involved in transcription regulation in the nucleus of normal cells.
Frontotemporal dementia (FTD) is a type of dementia that affects the frontal and/or temporal lobes of the brain. These are the areas of the brain responsible for personality, behavior, judgment, language, and movement.
The main symptoms of FTD include changes in personality and behavior, problems with judgment and planning, difficulty with language, and problems with movement. FTD may also cause changes in eating habits and sleep patterns.
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