Alzheimer’s disease – plaques, tangles, causes, symptoms & pathology

Alzheimer’s disease – plaques, tangles, causes, symptoms & pathology


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 chemically “sticky”, and bond together just outside
the neurons, and form what are called beta-amyloid plaques—these 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 disease–neurofibrillary 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.

100 thoughts on “Alzheimer’s disease – plaques, tangles, causes, symptoms & pathology”

  1. Thank you for your work! I can't understand why professors in expensive universities can't teach like this.

  2. I wonder people with Alzheimer disease only remember bad words, so many elderly that I heard suffering from Alzheimer and so sad they don't remember their family, they became angry rude and satanic!

  3. THANK YOU SO MUCH I WAS SO CONFUSED BUT THANKS TO YOU GUYS IM NOT ANYMORE
    I also really like the drawings and the animation it was a big help for me to understand! really good job I hope you continue your great work!

  4. Very clear, concise, and concrete. I looked at the First Aid book and everything said in this video and some correlated with the material. I will starting these videos more often to take my understanding and studying to another level. Thank you!!

  5. can sb explain to me how to 8:05 ''biopsy after autopsy'' since autopsy is already post-mortem
    ????????????

  6. Plaques and inflammations are caused by calcium shards floating through the bloodstream. These are liberated chunks of bone which accompanies bone loss; many elderly have fragile bones. Vitamin D-3 (Cholecalciferol) causes the bone loss AND the calcium shards which can also lead to chest pains, heart artery blockage, and other diseases caused by calcium building up in the wrong place. D-3 is not a vitamin, but a statin drug. It is the only active ingredient in rat/mouse poison. In 2013 the amount of D-3 added to milk was increased (Doctors are not your friends). Good news! The negative effects can be somewhat and slowly reversed: 1) STOP taking D-3 (no dairy; check your supplements). 2) start taking vitamin K-2 which selectively liberates calcium from the place it does not belong (brain, heart, eyes). Better yet, start eating fermented cabbage dishes like unpasteurized sauerkraut. This will give you K-2 plus probiotics for better digestion. Probiotics can sell for $40, whereas sauerkraut in a bag sells for $4.

  7. Such a great video! loved it very much it sums up my one hour long and boring lecture into just 8 minutes with the exact same amount of content! Can't believe they're ppl who actually disliked this video WHY?!

  8. How does all this end up decreasing ACh levels? I'm just wondering the patho behind why they have to be on cholinesterase inhibitors like donepezil or rivastigmine. Thanks!

  9. The definition of short term memory is wrong here. Remembering what sb had for breakfast belongs to long term memory. Short term memory is about your attention capacity in a specific moment, e.g. trying to remember a phone number sb just told you so that you can write it down.

  10. Great summary, very informative! What about the benefits of a Healthy diet, Exercise and Happy social relations? Surely that must play a role in maintaining brain cells

  11. So Plaques, Tangles, and a Shrinking brain are the RESULTS of Alzheimer's, all useless information, without the CAUSE!!!!!!!

  12. I have a doubt…..
    Brain biopsy after autopsy what does that mean 🤔
    Autopsy is done on dead bodies right

  13. I usually like yall's content, but sometimes I feel that is too detailed yet, too fast. Reinforce basics – Basic patho, diagnostics, treatment, and prognosis.

  14. Alzheimer disease nobody knows how it started no doctor no one it has only to do with decades of unhealthy diets high carb sugars and life style if you change that you won’t get Alzheimer’s healthy Keto diet and intermittent fasting is the solution and you will see what happens Pharma and doctors 🥼 don’t trust these criminal institutions only trust yourself 😉

  15. I work as a PhD student in Neuroscience and Bioinformatics and I think your work it's pretty solid and good. Thank you guys!!!

  16. Junk video! Regurgitation of the conventional NIH understanding of AD that serves to perpetuate mystery, confusion, and hide good research and understanding currently going on by neuroscientist and medical Dr. Dale Bredesen.
    Bredesen and Harvard's Tanzi have uncovered the real how and why of Amyloid Beta.
    I could say so much more but I'll stop.
    Very disappointing and behind the times video!

  17. Hat's off to you guys.. Thanks for such selfless work!
    Nowadays.. I hit like button before seeing this awesome video's.
    Thanks again. 😊

  18. Great explanation of neuropathology of Alzheimer's! I wonder if your estimation of prevalence in the over 85 age group is a bit inflated though. where did you get that stat? 50% is huge and certainly not the case in australia, where I live.

  19. Thanks so much for this video dude , You don't have a idea of how your explication help me.

  20. Alzheimers is only a Name of the person Alois Alzheimers who found in elderly shrinking brain tissue all doctors in 2019 say there is no cure they are totally wrong in early stages you can reverse this state of cognitive decline to normal look at Dale Bredesen the end of Alzheimers it has all to do with lifestyle and healthy diet and do get your body get rid of all the toxins !

  21. Great work team osmosis ❤aplausable job. U are giving education to lots of students across the world. 😇

  22. My great great great grandmother Nana Louder milk had this disease is Alzheimer's disease.☺😊😀😁😂😃😄😅😆😇😉🙌🙋👵💀👍👐👏

  23. A bunch of bullshit for the tin hat wearers! Our ancestors did not endure any of these diseases because they lived in a clean environment, drank clean, atresian, spring water not fluoridated water. They ate clean natural foods not doused in pesticides or full of chemical preservative, n artificial ingredients. And didn't use all kinds of chemical laden products on a daily basis. People don't be so ignorant to believe that this is generic or its so mysterious that it just came out of nowhere!

  24. I work years with Alzheimer's and Dementia patients with Alzheimer's or brain get too overloaded with memory and there's no more space we don't have unlimited memory it gets full quick nowadays with all the stuff we have computers movies Technologies it's overloading us quick that's why it's so rampat today that part of our brain that people say we don't use is being used it's being used for memory but we are filling it up quick compared to say 200 years ago and what's dementia your brain somehow goes in rewind you start going back in time young kid you think your parents are alive he thinks your brothers and Sister Wives you are a different time because your brain with rewind to that point and then you're a baby you cry call Mama daddy and somehow it's probably because it's over. And slowly starts with winding or something has happened yes brain injury causes some of these problems but most of it is from over full memory anything with memory has a full point just like if you would say a computer and it runs out of memory you have to delete stuff to put more memory in but we can't do that yet with our brains the best solution would probably be to cut out so much things maybe learning too much so quick black computer movies video games cause it to overload quickly and brain injuries probably cause some of the others rewind to forget

  25. I would imagine that research teams working directly or indirectly for big pharma would ignore any obvious preventions or lifestyle factors for which no medication could ever be involved …probably if researchers noticed it and tried to get traction it would be a very bad career move ….but then my wife tells me I am overly cynical of my fellow man

  26. How can modest drinking of alcohol have a dramatic (or notable at least) positive impact on their likely hood of falling victim to this crap? I read this and then checked if Mormons have more Alzheimer's (they don't drink) sure enough ….YEP Salt Lake news article verifies the residents (a LOT of them Mormons) have significantly higher incidence of ….So guess what? I now have 2 drinks per day…cause I am so paranoid I am prone to it….

  27. Please read the book by Valery Mamonov Ph.D titled " NUTRITION MYSTERY SOLVED:
    , WHY JAPANESE RESEARCHERS WOULD NEVER EAT
    FRIED FOOD" sold at Amazon. com at $6.99 only. This book reveals how oil and fat play a huge role in managing the disease. Coming from a family with a history, this book is a miracle for me.. I hope it helps you too.

  28. Thank you for making me clear .. but the biology behind alzheimer was quite tough .. like the names of proteins and all. But still this video worth my time ..

  29. Out of interest – how close is your WiFi router to where you sleep or sit in the day? I am researching the dangers and effects of EMF radiation. Also do any patients have a history of using mobile device data (3G 4G). Try out an EMF meter – there are videos on YouTube showing the levels around mobile phone masts, mobile devices using data and WiFi routers. The on set of young dementia is increasing and I am seeing a correlation between the two as well as some cancers. I have not yet finished my research so have no real evidence apart from the fact that everyone has a mobile and most homes have a more and more powerful WiFi router not to mention the baby monitors that people put right next to a newborn baby that is basically a powerful radio right next to their head. It makes you really wonder what all of this is doing? Thank you for any information and reply. You can always hard wire your router and use a cable to connect your PC and turn off the radio part of the router. Also putting your mobile device in airplane mode is advised when not using it. Lots of things we can do. But you can have no idea if when you sleep, a neighbours WiFi router is only just through the thin wall right next to your head. Use an EMF Radiation meter and you will be surprised at how high the level is way over the recommended level. Please let me know if any patients have used a mobile phone. Thank you.

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