3.3.1 Alzheimer’s disease: introduction and myths

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En provenance du cours de Peking University

Advanced Neurobiology I

252 notes

Peking University

Advanced Neurobiology I

252 notes

Hello everyone! Welcome to advanced neurobiology! Neuroscience is a wonderful branch of science on how our brain perceives the external world, how our brain thinks, how our brain responds to the outside of the world, and how during disease or aging the neuronal connections deteriorate. We’re trying to understand the molecular, cellular nature and the circuitry arrangement of how nervous system works. Through this course, you'll have a comprehensive understanding of basic neuroanatomy, electral signal transduction, movement and several diseases in the nervous system. This advanced neurobiology course is composed of 2 parts (Advanced neurobiology I and Advanced neurobiology II, and the latter will be online later). They are related to each other on the content but separate on scoring and certification, so you can choose either or both. It’s recommended that you take them sequentially and it’s great if you’ve already acquired a basic understanding of biology. Thank you for joining us!

À partir de la leçon

Cellular and Molecular Biology of the Neuron

Let‘s continue with the neuron.

3.3.1 Alzheimer’s disease: introduction and myths15:02

3.3.2 Alzheimer’s disease: pathology7:36

3.3.3 Parkinson’s disease: introduction0:52

3.3.4 Parkinson’s disease: symptoms and prognosis9:47

3.3.5 Parkinson’s disease: pathology3:12

3.3.6 Parkinson’s disease: treatment15:36

3.3.7 Prion diseases14:21

Rencontrer les enseignants

Yan Zhang
Professor
School of Life Sciences, Peking University
Yulong Li
Research Fellow
School of Life Sciences, Peking University

So today, we'll talk about some disease and

we try to understand physiological processes through diseases.

And the first disease we're going to talk about is Alzheimer's disease.

There are several diseases in the nervous system that is associated

with protein aggregation, mislocation of these proteins

and the big aggregates formed inside of the cell.

So these diseases include Alzheimer's disease and Parkinson's disease.

So in Alzheimer's disease inside of the neuron,

we have aggregates formed with hyperphosphorylated tau protein.

The black staining labeled here.

And if we take a close look of these aggregates,

we'll see these paralleled filament inside of the cellular structure.

So we call it a paired helical filaments inside of the cell.

And in Alzheimer's disease, we have another kind of cellular

aggregates formed outside of the cell extracellularly.

And it formed with amyloid beta peptide and made

these amyloid plaques or senile plaque.

In the Parkinson's disease we have also a structure called Lewy body inside of

a cell, its aggregates formed with alpha-synuclein.

So studying the disease is a way to understand a normal process or

the normal physiology.

The dementia, Alzheimer's disease is the most common form of dementia.

Dementia is a group of brain cells that die eventually and

that will lead to loss of memory and mental function.

Besides Alzheimer's disease, we also have some other types of dementia.

For example, vascular dementia.

It's related to lack of blood flow of certain brain areas,

induces the neuronal cell death in that particular brain area.

So in Alzheimer's disease and vascular dementia,

sometimes they can happen together in some brain area, so we call it mixed dementia.

So mixed Alzheimer AD type of dementia and vascular dementia.

And other causes of dementia include frontotemporal dementia and

dementia with Lewy body that often happen in

the late stage of Parkinson's disease and

CJD caused by infection of prion particle.

Alzheimer's disease is named after Dr. Alzheimer, and this is Dr.

Alzheimer and this is the patient he first described that has this kind of dementia.

So Alzheimer's diseases is a progressive brain disorder,

gradually destroy a person's memory and ability to learn, to reason,

to make judgment, communicate and carry out daily activity.

In the late stage of Alzheimer's disease, people can have some personality change

and some behavioral symptoms like anxiety, suspiciousness and

illusion and hallucination.

So if we compare the brain of Alzheimer's disease

patient to the age matched control,

we'll see dramatic shrinking of the volume of the brain.

So that suggest massive cell loss happened in Alzheimer brain.

So the progression of this disease, it can last pretty long.

Sometimes it can last for 20 years and

then the area controlling memory, learning and

memory get destroyed, get affected first.

And then it gradually,

it progressively affects the brain area close to that area.

So if we look at this picture, so entorhinal cortex and

hippocampus are the first two brain area that are affectedin AD, Alzheimer's disease.

The light blue region here, and

then because it is a kind of neurodegenerative disease.

So that means a group of neuron die and then the other group of neuron that

have the synaptic connection with this group of neuron die after.

And in just like the death signal spread to the brain area close by.

So the brain area close by the neuron in those area die.

And then eventually, in advanced stage, In the late stage of the disease,

lots of the gray area can be affected, including the frontal lobe

and sometimes can be the visual cortex.

So what is the cause of disease?

We still don't know what is exactly cause of this disease.

We see some symptom, we see some pathological markers of this disease.

One is called plaque and then the other one is called tangle.

The plaque is made of amyloid beta peptide and it's extracellularly.

And a tangle is intracellularly and is made with hyperphosphorylated tau protein.

So whether these pathological hallmarks are the cause of the disease or

just simple consequence of the disease, we still don't know.

So in this picture, inside of the cell, inside of the neuron,

we have neurofibrillary tangle made of tau protein.

And then outside of the cell we have senile plaque,

made of amyloid peptide and this two things can induced neuronal cells death.

There are several risk factors for this disease.

One of course is age.

So the incidence of this disease at age over 65 is around 5%.

If the age is over 85, the risk reaches to near 50%,

so nearly one in two elderly over 85

will have Alzheimer's disease.

Family history of the genetics, we do have some some families or

some patients that carry familial mutations of this disease.

And the paths to prevention, we don't have effective

prevention now because we don't understand how this disease happens.

So we don't have a clear target for therapy or for prevention.

So all this data sometimes comes from statistics,

sometimes are quite controversial.

So gene and environment, so which one contribute to the disease more?

We still don't know.

There are in the whole disease population,

we have around 5% that carry familial AD mutations and

the other 95% are sporadic, meaning there is

no clear genetic mutations in those 95% patient.

Head injury, if you have trauma or head injury,

your risk of having Alzheimer's disease increases.

And then head and heart connections,

if you have a disease in the vascular

system that you risk of having

Alzheimer's disease increase.

There are some misunderstanding of this disease.

One is the memory loss is Just a natural part of aging.

As you age, as you are getting older your memory will get worse and worse.

Well that's kind of true, but

does not totally true there's distinct

differences between Alzheimer's,

dementia and age related memory change.

I listed the comparison of the two here.

So for the Alzheimer's disease the forgetting

can be the entire experience and for

age related memory decline it's just part of

an experience it cannot be the whole event as a whole.

For Alzheimer's disease, if you forget it's rarely that you can remember later.

But for age related memory decline,

sometimes you can still recall the event later, and

there's another misunderstanding that this disease is not fatal.

While it is true, it doesn't kill the patient by itself,

but sometimes it can lead to some accidents of the patients.

For example, in the late stage of

the Alzheimer's disease people cannot memorize the details or

cannot memorize some common sense of life.

He may not remember that fire can be harmful and

then he can touch the fire by hand, just by hand and that's an accident.

And it happened very often the Alzheimer's disease

patient can go out of the street and easily get lost on the street.

So this disease can easily cause all kinds of accident that will sometimes be fatal.

And then the link, or association between

aluminum and Alzheimer disease is negative.

Well the rumor of aluminum, the correlation of aluminum and

Alzheimer's disease came from a study with a small group of person.

And then one person repeated that experiment

with large population, with large sample size.

And then the data or the results are not repeatable.

For Alzheimer's disease per se The amount

or the level of aluminum doesn't correlate with the incidence of the disease,

but intaking too much aluminum is not good for health.

So another needs understanding is that there are several things

available to stop this disease, but as we just mentioned because we

don't understand the pathological process of this disease.

We don't know how the neurons die in this disease.

So there is no effective drugs we can use.

There are some drugs that are approved by FDA that can improve the symptoms,

and that includes cholinesterase inhibitors.

Because in the disease, in early stages of this disease,

lots of the neuronal death happened in

cholinergic neurons in hippocampus.

So the cholinesterase is an enzyme

that can kill the acetylcholine.

So use the inhibitor to this enzyme can kind of improve the symptom.

Memantine is an antagonist to NMDA receptor,

and the effect of this drug is general.

It's not specific to AD itself.

Too much neuronal excitation can induce glutamate toxicity.

So memantine simply decrease the chance

of having this glutamate toxicity.

Vitamin E is another general drug, it is

not only specific to AD as well.

It is an antioxidant, and it increase the general health of the brain.

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