Alzheimer's disease - plaques, tangles, causes, symptoms & pathology

Follow us on social:

Our Vision: Everyone who cares for someone will learn by Osmosis.

© 2024 Elsevier. All rights reserved.

[ravykiran]

You guys have no idea how many students are being helped by your you Osmosis.

[auxilium]

My grandmother had Alzheimer's. I remember her looking at an old picture of her and my grandfather, pointing at it and saying "He left me" He didn't leave her. He died in 2012 and she forgot due to her illness. She died in September 2018 only 2 months away from becoming 90. Diseases that cause memory loss are things I wouldn't wish upon my worst enemy.

[mrunalinideonikar]

it's the best video on Alzheimer I've ever seen. it helped me in my exams alot. Thanks

[joshbates]

In December of 2001, My father was diagnosed of Alzheimer's disease. We saw it coming where as his first symptoms were in Late-2000. By April of 2006 he got Bad, In 2008 he got to the point where my mom or family members couldn't take care of him so we had to put him in a Home. By Early 2010, He had no idea who we were his sons, Grandchildren, Even my mom (His wife) He only knew who his best friend 'Stanley' was (Friends for 85 years)
It was extremely heart-Breaking and very saddening the one who raised me had no idea who i was nor my mom who he was married to since 1945 (65 years at that time) he was heading downhill very fast, Faster than usual the doctors said. Unfortunately On January 11, 2011 he passed away he was 93 years old.
Alzheimer's isn't only disease but its one where memories are forgotten from your loved one. Where as times your closest role model doesn't even know who u are.

[RohitPant]

Hands down, the most concise and simple explainatory video on All i have seen online. Like always, thanks!

[SteveWoodyMusic]

For those interested, I made a full transcript of this video. Hope this helps someone else out, especially those writing papers! I double checked everything, but please let me know if I missed anything.

"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 is caused by some sort of damage to the cells in the brain which can be caused by 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 in tangles.


All right, so here we've got this 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 overtime it gets broken down and recycled. Normally, it gets chopped up by an enzyme called Alpha secretase and its buddy, Gamma secretase. This chopped up peptide is soluble and goes away and everything is all good. if another enzyme, beta secretase, teams up with gamma secretase instead then we've got a problem. This leftover fragment isn't soluble and creates a monomer called amyloid beta. These monomers tend to be 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 the 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 cells. 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 that essentially act like a minecart shipping nutrients and molecules along the length of the cell. A special protein called Tau makes sure that these tracks don't break apart, kind of like railway ties. Although again it's not completely understood, it's thought that the beta amyloid plaque buildup outside the neuron initiates pathways inside the neuron that lead 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 and gets tangled and leads to the other characteristic finding of Alzheimer disease, neurofibrillary tangles.


Neurons with tangles in 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 neuron. 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 groups between the Gyri, get wider. With atrophy the ventricles, or fluid filled cavities in the brain, get larger as well.


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 is 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. And sporadic accounts for the vast majority of cases. With sporadic Alzheimer's, the risk increases significantly with age affecting around 1% of people between ages 60-65 and 50% of people over the age of 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 breakdown beta amyloid, but the E4 allele seems to be less effective than the other alleles like the APOE 2 allele, meaning patients are more likely to develop beta amyloid plaques.


Familial Alzheimer disease, on the other hand, is used to describe cases where some dominant gene was inherited that speeds up the progression of the disease. So, sometimes familial Alzheimer's disease is referred to as early-onset Alzheimer's. Familial accounts for about 5 to 10% of cases and could be caused by several gene mutations. First, mutations in the PSEN-1 or PSEN-2 genes on chromosome 14 or chromosome 1, respectively, had been linked to early-onset Alzheimer's. These genes encode for presenilin 1 and 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 presumably increased expression of APP, potentially increasing the amount of amyloid plaque buildup. For this reason, familial Alzheimer disease often progresses by age 40 in patients with Down Syndrome.
Symptoms of Alzheimer disease worsen as plaques and tangles buildup and damage to the neurons accumulates. In the early stages, symptoms might not even be detectable. As it progresses, though, patients lose short-term memory. Like, for example, they might not be able to remember what they had for breakfast that morning. They then progress to a 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 in the 1st place. And they progressively become more disoriented, which can be dangerous because they might wander from home and get lost.
In the late stages 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."

[dr.delcyshealingzone]

Osmosis, thank you for existing. You can't even imagine how much you guys have helped me to clear my annual exams in medical college. Every prof was so easy because of you and I never had to have sleepless nights to study and cram diseases from books, your videos were enough for me to write about a disease in exams. Please never stop making content. I will always watch your videos despite being a practicing physician.

[hah-no.]

My grandpa had this and he was an amazing man. I wish I had spent more time with him. May he Rest In Peace, and thank you for educating thousands of people and helping them grow. Keep doing what you’re doing! 🤍

[drkhan]

I don't know how many lecturers are delivering lectures at the osmosis but the person in this lecture is the best among all. He delivers the information so beautifully that i love to listen and is very easily understood and retained. Thank you so much sir 👍

[Melzare]

Got a neuro exam tomorrow so going through your videos as a refresher. They’re well made, thanks a ton!

[oura]

Oh my god
Our professor took 3 hours explaining that desease and we have not understood almost anything
But you with that video in 9 minutes made it really simple and clear
Man you are extremely genius
You are talented
Thank you so much 💙💙💙💙

[sf]

thankyou so much!simplifying a textbook chapter and numerous lectures into 8 minutes!

[jennamichelle]

My grandmother has Alzheimer’s or dementia. Once she didn’t recognize photos of her deceased husband, and has forgotten what relation my deceased father (her son) was to her. I hope that one day Alzheimer’s and all other forms of dementia will be cured. 💜

[aeensamp]

My mother passed way at the age of 39 the doctor didn't get the disease but the symptom is related to this...
It was really heartbreaking ....She didn't even know us
My 7 year old brother and 16 year me
didn't even got a chance to say a last goodbye to
I wish i had a chance to show that how much i love her

[maxzellblackwell]

I finally understand the actual biology behind this disease. Life saver for my final!!!

[jacocksc]

Incredibly helpful with an excellent presentation. Thanks so much!

[iSedma]

These are by far the most helpful medical videos I've come across! I love how concepts are clearly and concisely explained, relevant information included. I got more from these 10min videos than from hours of lecture and reading textbooks. Thanks so much, you guys are doing an incredible job!

[AutopsyMyDeath]

My Ukrainian grandfather had Alzheimer's disease and he was a professional violinist. When i was a kid he played with the violin every day and i remember hearing him get frustrated and swearing in Ukrainian since he was slowly forgetting all the Ukrainian folk songs he loved because his of Alzheimer's was slowly getting worse... Horrible to witness as a kid. He passed away in 2010 and i miss him so much....

[codydudgeonphysiotherapy]

Thank you for putting a lot of time, effort and detail into this video. As a Physiotherapist, on my new channel I am trying to educate as many people as I can on Alzheimer’s disease and dementia. I put up a video telling people that forgetting why you entered a room is a normal part of aging, and to not worry yourself about it. Let’s keep up the good work together and keep the videos coming!

[utkarshdubey]

When it comes to neurology, we all are helpless as these diseases don't have a definitive cure.
Hope this field grows faster!