Placeholder Image

字幕表 動画を再生する

  • Dementia isn't technically a disease, but more of a way to describe a set of symptoms

  • like poor memory and difficulty learning new information, which can make it really hard

  • to function independently.

  • Usually dementia's caused by some sort of damage to the cells in the brain, which can

  • be from a variety of diseases.

  • Alzheimer's disease, now referred to as Alzheimer disease, is the most common cause

  • of dementia.

  • Alzheimer disease is considered a neurodegenerative disease, meaning it causes the degeneration,

  • or loss, of neurons in the brain, particularly in the cortex.

  • This, as you might expect, leads to the symptoms characteristic of dementia.

  • Although the cause of Alzheimer disease isn't completely understood, two major players that

  • are often cited in its progression are plaques and tangles.

  • Alright, so here we've got the cell membrane of a neuron in the brain.

  • In the membrane, you've got this molecule called amyloid precursor protein, or APP,

  • one end of this guy's in the cell, and the other end's outside the cell.

  • It's thought that this guy helps the neuron grow and repair itself after an injury.

  • Since APP's a protein, just like other proteins, it gets used and over time it gets broken

  • down and recycled.

  • Normally, it gets chopped up by an enzyme called alpha secretase and it's buddy, gamma

  • secretase.

  • This chopped up peptide is soluble and goes away, and everything's all good.

  • If another enzyme, beta secretase, teams up with gamma secretase, then we've got a problem,

  • and this leftover fragment isn't soluble, and creates a monomer called amyloid beta.

  • These monomers tend to be more chemicallysticky”, and bond together just outside

  • the neurons, and form what are called beta-amyloid plaquesthese clumps of lots of these monomers.

  • These plaques can potentially get between the neurons, which can get in the way of neuron-to-neuron

  • signaling.

  • If brain cells can't signal and relay information, then brain functions like memory can be seriously

  • impaired.

  • It's also thought that these plaques can start up an immune response and cause inflammation

  • which might damage surrounding neurons.

  • Amyloid plaque can also deposit around blood vessels in the brain, called amyloid angiopathy,

  • which weakens the walls of the blood vessels and increases the risk of hemorrhage, or rupture

  • and blood loss.

  • Here's an image of amyloid plaque on histology, these clumps are buildups of beta amyloid,

  • and this is happening outside the cell.

  • Another big part of alzheimer disease are tangles, and these are actually found inside

  • the cell, as opposed to the beta-amyloid plaques.

  • Just like other cells, neurons are held together by their cytoskeleton, which is partly made

  • up of microtubules, these track-like structures essentially act like a minecart shipping nutrients

  • and molecules along the length of the cell.

  • A special protein called tau makes sure these tracks don't break apart, kind of like railway

  • ties.

  • Although again, not completely understood, it's thought that the beta amyloid plaque

  • build-up initiates pathways inside the neuron that leads to activation of kinase, an enzyme

  • that transfers phosphate groups to the tau protein.

  • The tau protein then changes shape, stops supporting the microtubules, and clumps up

  • with other tau proteins, or gets tangled, and leads to the other characteristic finding

  • of Alzheimer diseaseneurofibrillary tangles.

  • Neurons with tangles and non-functioning microtubules can't signal as well, and sometimes end

  • up undergoing apoptosis, or programmed cell death.

  • Here's an image of histology showing these neurofibrillary tangles formed inside the

  • cell.

  • As neurons die, large scale changes start to take place in the brain, for one, the brain

  • atrophies, or shrinks, and the gyri get narrower, which are the characteristic ridges of the

  • brain.

  • As those get narrower, the sulci, which are the grooves between the gryi, get wider.

  • With atrophy, the ventricles, fluid-filled cavities in the brain, get larger.

  • So that's the pathophysiology part, but why does this happen in some people and not

  • others?

  • Well Alzheimer disease can be split into two groups - sporadic and familial.

  • Sporadic's used to describe the late-onset type where the exact cause isn't very well

  • defined, and is probably a combination of genetic and environmental risk factors.

  • Sporadic accounts for the vast majority of cases.

  • With sporadic Alzheimer's, the risk increases significantly with age, affecting around 1%

  • of people age 60-65, and 50% of people over age 85.

  • In fact, a gene that's been identified as possibly contributing to an increased risk

  • of alzheimer disease is the e4 allele of apolipoprotein E gene, or APOE-e4.

  • Researchers have shown that the risk of developing alzheimer disease increases for patients that

  • inherit one e4 allele, and increases even more for patients who inherited two e4 alleles,

  • one from each parent.

  • Apolipoprotein E helps break down beta-amyloid, but the e4 allele seems to be less effective

  • than other alleles, like the APOE-e2 allele, meaning patients are more likely to develop

  • beta-amyloid plaques.

  • Familial alzheimer disease is used to describe cases where some dominant gene was inherited

  • that speeds up the progression of the disease, so sometimes familial alzheimer disease is

  • referred to as early onset Alzheimer's.

  • Familial accounts for between 5 and 10% of cases, and can be caused by several gene mutations.

  • First, mutations in the PSEN-1 or PSEN-2 genes genes on chromosome 14 or chromosome 1, respectively,

  • have been linked to early-onset Alzheimer's.

  • These genes encode for presenilin-1 or presenilin-2, both protein subunits of gamma-secretase.

  • Mutations in these PSEN-1 or PSEN-2 genes can change the location where gamma secretase

  • chops APP, producing different length beta amyloid molecules, which seem to be better

  • at clumping up and forming plaques.

  • Another known genetic cause of Alzheimer's is trisomy 21, or down syndrome, which involves

  • an extra copy of chromosome 21.

  • It turns out that the gene responsible for producing APP is located on chromosome 21,

  • which means that people with down syndrome have an extra APP gene, and so presumably

  • increased expression of APP, and possibly increased amounts of amyloid plaque.

  • For this reason, familial Alzheimer disease often progresses by age 40.

  • Symptoms of Alzheimer disease worsen as plaques and tangles build up, and neuronal damage

  • accumulates.

  • In the early stages, symptoms may not even be detectable, as it progresses, patients

  • lose short-term memory, like for example they may not be able to remember what they had

  • for breakfast that morning.

  • They then progress to loss of motor skills, making things like eating difficult without

  • help.

  • Also language becomes affected, making it more difficult to communicate.

  • Eventually they lose long-term memory, like forgetting the name of their spouse or even

  • that they're married, and progressively become more disoriented, which can be dangerous,

  • because they might wander from home and get lost.

  • In late-stage, they become bedridden, and the most common cause of death is actually

  • infection, like pneumonia.

  • Diagnosis of Alzheimer disease is really tough, because the only way to definitively show

  • that a person had Alzheimer's is by performing a brain biopsy after autopsy.

  • Usually a clinician will therefore make a diagnosis after excluding other causes of

  • dementia.

  • Currently, there isn't any cure for Alzheimer disease, some medications exist, but the benefits

  • are small and there haven't been any medications that clearly and definitively halt the progression

  • of Alzheimer's.

Dementia isn't technically a disease, but more of a way to describe a set of symptoms

字幕と単語

動画の操作 ここで「動画」の調整と「字幕」の表示を設定することができます

B2 中上級

アルツハイマー病 - プラーク、もつれ、原因、症状、病理学 (Alzheimer's disease - plaques, tangles, causes, symptoms & pathology)

  • 318 31
    memory15728 に公開 2021 年 01 月 14 日
動画の中の単語