Alzheimer’s Disease: biochemical changes in AD brain

In an earlier post, I discussed the structural changes caused by Alzheimer’s disease, that make AD brains different than normal brain. But the plaques and tangles that appear in AD brain only tell part of the story. There are also changes occurring in the biochemistry of AD brains.

Neurotransmitters are reduced

Healthy hippocampal neuron

Hippocampal pyramidal cell

Chemical messenger molecules (neurotransmitters) are reduced in the AD brain. These neurotransmitters carry information (signals) from one neuron to the next. There are many different neurotransmitters. Some transmit basic information. Others either amplify of decrease the strength of the signal sent. Most brain regions use several different neurotransmitters. Like the physical changes which occur in AD, decreases in neurotransmitters occur first in brain areas associated with learning and memory, such as the hippocampus and cortex.

Changes in the cholinergic system

The first neurotransmitter found to be reduced in AD was Acetylcholine (a-see’-til-ko’-leen). Brain neurons releasing the neurotransmitter acetylcholine are called cholinergic (ko’-lin-er’-jik) neurons. Together they make up the cholinergic system, which is the earliest and arguably the most severely affected neurotransmitter system in AD.

Although acetylcholine is not the only neurotransmitter used in the hippocampus and cortex, it plays a crucial role in learning and memory processes in those areas.

The role of cholinergic neurons

Cholinergic neurons encourage other neurons in the hippocampus and cortex to transmit messages. When the cholinergic system is not functioning properly, the other neurons are less likely to pass messages on. This interferes with both learning and remembering.

Other biochemical changes

Other biochemical molecules are also affected by Alzheimer’s disease.

Some researchers find that growth-promoting molecules which would normally support the health of neurons are either decreased or ineffective in the Alzheimer brain. This may partly explain the large number of neurons and neuron connections (synapses) that are lost.

Other scientists have found a lack of growth-inhibiting molecules in the AD brain, and think a lack of appropriate inhibition may help explain the growth of abnormal neuronal fibers inside cell bodies and the growth of neuronal processes that curl randomly about instead of making proper synaptic contacts.

The ultimate significance of changes in growth-promoting and growth-inhibiting molecules is not yet clear.

The role of Alzheimer’s Research

Many researchers are involved in the fight against AD, but progress has been slow. The disease has been identified since 1904 when it was first described by Dr. Alois Alzheimer. Following the publication of Dr. Alzheimer’s initial description, the physical changes this disease caused in the brain were quickly and thoroughly catalogued. However, it took nearly 70 years, and the development of new research techniques, before a way to do more than just describe the symptoms was found.

In the years from 1986 to now, the pace of research in AD has increased. Still, because AD is probably the result of an accumulation of contributing factors, we may never identify a single simple cause for it.

More than just scientists

Biomedical research is more than just a job, and the biomedical researchers studying Alzheimer’s disease, are more than just scientists.

These men and women have chosen, from the whole world of medical research, to tackle problems affecting the most complex of all systems, the human brain. Driven not only by the desire to understand, but also by the desire to help, biomedical researchers share a need to have their work impact the lives of people. They want to make a difference. They are people with a mission.

Occasionally I will discuss new findings in scientific research. But I also want to give you the opportunity to recognize the people behind the work—people who, although you may never meet them or even know their names, are standing shoulder to shoulder with you in the fight against this debilitating disease. I hope that when you read about the work these men and women do, you will see more than just the advancement of science. I hope you will realize you are not alone.

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Neurons: You know you’ve got them, but what are they, really?

Neurons are one of two main groups of cells in the brain: neurons and glia. Neurons and glia differ in structure and in function, but both are absolutely essential to the work of the brain.

Two neurons on a bed of glial cells

Two neurons (with halos) on a bed of glial cells

Functions of neurons

Neurons pass along information. When you look at the text on this page, your eyes send electrical impulses to brain neurons. An impulse received by one neuron is passed onto the next and the next in a kind of electrical bucket brigade, which is interpreted by the brain as words. A simple message, like that of the knee jerk reflex, may be carried by only two neurons. But most messages require from thousands to millions of neurons working together to convey the information.

Functions of glia

Glia, also called glial cells, are support cells. Each neuron in your brain has 10 to 50 glial cells helping to care for it. Since you were born with 100 billion neurons (roughly the same as the number of stars in the galaxy), that means you have one to five trillion glial cells.

Glia

Glia

These cells surround neurons, offering physical and nutritional support. They surround synapses and play a (recently-discovered) role in enhancing synaptic transmission. They encase neuronal axons, speeding the transmission of information within the neuron. And they form the blood-brain-barrier, which can protect the brain by denying blood-borne pathogens access to it.

Neuronal structure

Every aspect of a neuron’s structure is designed to optimize its ability to transmit information. Most neuronal cell bodies are round or roughly triangular in appearance. Fine, threadlike processes stretch out from these cell bodies. Multiple processes called dendrites receive information coming into the neuron. The information, then flows through the cell body and down the transmitting arm of the neuron, called an axon. Most neurons have many dendrites for receiving information and only one axon for transmitting information.

[Random thought: Does this mean we should listen more than we talk?]

The axon passes information along to the dendrites of the next cell (or cells) in line. Neurons are built to last a lifetime, and in the healthy brain, they continue to grow by making additional connections throughout life.

Interconnected neurons

Interconnected neurons

The flow of information in the brain is dependent upon billions of interconnected neurons. Normally many neurons carry the same bit of information simultaneously. That duplication insures that loss of a few neurons will not disrupt the flow of information. However, a continuing loss of neurons, such as occurs over time in many neurodegenerative disorders, will eventually overwhelm the brain’s fail-safe systems and interrupt the flow of information.

I hope this information interested you. If you want to share it, there are buttons for Twitter, Facebook, LinkedIn and Google plus below. Your brain is the most complex three pounds of matter on the planet. It beats out super-computers and everything else we have ever succeeded in building. Use it well!

Learn more about your personal super-computer, right here. From now on, every Friday will be Brain Day, and on Wednesdays I’ll make my usual posts about LIFE. Want my posts sent straight to your email? Hit the Follow button on the lower right corner of this page. And not to worry… I keep your email address private—no putting you on spam lists.

Alzheimer’s Disease: physical changes in AD brain

The underlying causes of the memory loss, confusion and disorientation of Alzheimer’s disease (AD) are complex, but not altogether unknown. This post describes the physical changes in the brain that underlie and contribute to the dementia of AD. Those changes occur in both the appearance and the connections of brain neurons. (To read about normal brain, for comparison, click here.)

Tangles and plaques in Alzheimer's brain

Normally, long threadlike structures called neurites extend from neuronal cell bodies and connect neuron to neuron in an organized pattern.

Looking through the microscope at an Alzheimer’s brain, researchers see that this pattern has been disrupted. In some areas, neurons have died and disappeared, leaving fewer cells available to carry information.

There are some neurons whose cell bodies are filled with twisted fibers—as if their neurites had become ingrown. Neurons filled with fibers like this are called tangles. They are the dark blue, spider-like objects in the picture above. Often, the neurites that reach out from these cells are abnormally short or are missing altogether. A few of the tangles, called ghosts, are already dead; their outside cell walls have disintegrated. The twisted clumps of fibers are all that remain.

Many neurons in AD brain have normal-looking cell bodies, but their neurites curl about in a random pattern, not making proper connections. Still other neurons have neurites that have become embedded in abnormal clumps of protein found outside the cells, instead of making normal connections with thier neighbors.

The abnormal clumps of protein found outside of cells are called amyloid plaques. These are the large, diffuse circular structures in the picture above. They are medium blue in color and are larger than the dark, spider-like tangles.  A small number of such plaques are found in the brains of healthy elderly individuals. However, individuals who have Alzheimer’s disease have many, many more of them–particularly in the areas of the brain involved with learning and memory.
The plaques contain a protein called beta-amyloid (or A-beta). In advanced cases of AD, beta-amyloid is also deposited in and around the blood vessels of the brain. That deposition is called cerebrovascular amyloidosis, or CVA.

Together, plaques and tangles interfere with the normal connections of brain neurons and contribute to the death of neurons in the AD brain.

Plaques and tangles, along with CVA and diffuse cell loss, are hallmarks of Alzheimer’s disease, and are easily observed in AD brain tissue. But they don’t even begin to tell the whole story. There are many other changes that occur in the AD brain and cause it to lose function. More on those next time.

Do you have questions?

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Brain Basics: a look at normal brain

There are some interesting things being learned in Alzheimer’s disease research these days. I’d like to talk about them, but you need to understand a little bit of brain biology first. So this is my plan…

I’m going to write a few posts on the basics of brain biology. And maybe a glossary of terms, too. If you are interested, learning about the basics should make it easier to make sense of what you read or hear about this disorder. If you already know the basics, think of this post as a review, or jump to the post on AD brain.  Once we get the basics out of the way, I’ll be able to talk about what research scientists are learning without making every post a tutorial.

So let’s start with the basics of what a normal brain looks like, and go from there:

The Human Brain

Silver-stained neurons

Under the microscope, the human brain presents a beautiful, yet silent landscape. Individual silver-stained neurons stand silhouetted against their surroundings like trees against a sunset. Their beauty, delicacy and orderliness have captured the minds and hearts of scientists for over a hundred years.

There are approximately 100 billion neurons in the brain, carrying and processing information. Several times that many other cells, called glia, feed and support the neurons. All these cells are serviced by a network of blood vessels ranging in size from large arteries to tiny capillaries. Organized into pathways, groups of neurons gather, process and respond to information from the outside world in ways that are similar for us all, yet unique to each.

Information comes to neurons through the senses, transmitted by specialized neurons, like the touch sensors in our skin or the rod and cone cells in our eyes. These sensory cells transform the input they receive into electrochemical messages.

The electrochemical messages are sent to the brain, where input from all the senses is combined. Some input is important and requires conscious attention. Some input is background, like the feel of clothing against your skin, and is not usually brought to our conscious attention. The brain decides automatically, based on experience, which input requires conscious attention and which does not.

We can change those automatic choices by focusing our attention on any part of the input we want. But to pay attention to all of it, all the time, would keep us too busy to get more important things done. The automatic choices made by the brain free us to think and create.

If sensory input requires a response—perhaps a verbal answer to a question or reflexively jerking your hand away from a too-hot frying pan—messages are sent back from the brain to the muscles that need to act. The number of neurons involved in this process can vary from as few as two (for the simplest reflex pathways) to whole networks of connected neurons numbering in the billions.

As a message travels through a network of connected neurons, it alternates between moving as an electrical signal and moving as a chemical signal. Within a neuron, messages are carried by changes in electrical charge that sweep from the receiving arms of the neuron (dendrites) through the cell body, to the transmitting arms (axons). Where one neuron’s transmitting axon meets another neuron’s receiving dendrite, special connection sites called synapses are formed. Messages are carried across synapses by neurotransmitters, the chemical messengers of the brain.

When a message is sent across a synapse, it is the amount of neurotransmitter released and received that determines the strength of the signal. In a normal, healthy brain, many synapses remodel themselves in response to the messages sent across. Synapses that are used frequently or that carry strong signals can actually become larger, while synapses that fall into disuse can shrink.

Completely new connections, new synapses, can be formed between two neurons in a pathway when frequent messages and strong signals pass between them. This would give you two synapses where there used to be only one, and would strengthen the message being carried by the pathway.

Interestingly, new synapses can also form when the loss of certain neurons in a well-used pathway has caused the neurons beyond them to become disconnected from the flow of information.  In this case, neighbors of the lost neurons sometimes sprout new transmitting arms (axons) that reconnect the downstream neurons to the information flow.

Remodeling of synaptic contacts and the formation of new synapses form the basis for learning and memory. Pathways that are often used grow larger, stronger synapses and we remember the information that they carry more easily.

Neurons make new synapses most frequently when we are young, probably because we are learning so many things at that time. However, the ability to make new synapses and remodel old ones continues in the healthy brain throughout life.

Whew!         Any questions??         Talk to me!

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