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What Are the Main Characteristics of AD?: Structure and Function of the Brain

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By 1999 Progress Report by the NIA/NIH • • December 13, 1999

The brain does many things to ensure our survival. With the help of motor and sensory nerves outside of the brain and spinal cord, it integrates, regulates, initiates, and controls functions in the whole body. The brain governs thinking, personality, mood, the senses, and physical action. We can speak, move, remember, and feel emotions and physical sensations because of the complex interplay of chemical and electrical processes that take place in our brains. The brain also regulates body functions that happen without our knowledge or direction, such as digestion of food.

The human brain is made up of billions of nerve cells, called neurons, that share information with one another through a large array of biological and chemical signals. Each neuron has a cell body, an axon, and many dendrites, all surrounded by a cell membrane. The nucleus, which contains genes composed of deoxyribonucleic acid (DNA), controls the cell's activities. The axon, which extends from the cell body, transmits messages to other neurons, sometimes for very long distances. Dendrites, which also branch out from the cell body, receive messages from axons of other nerve cells or from specialized sense organs. Axons and dendrites collectively are called neurites. Even more numerous are the glial cells, which surround, support, and nourish neurons.

Neurons communicate with each other and with sense organs by producing and releasing special chemicals called neurotransmitters. As a neuron receives messages from surrounding cells, an electrical charge (nerve impulse) builds up within the cell. This charge travels down the nerve cell until it reaches the end of the axon. Here, it triggers the release of the neurotransmitters that move from the axon across a gap between it and the dendrites or cell bodies of other neurons. Scientists estimate that the typical neuron has up to 15,000 of these gaps, called synapses. The neurotransmitters bind to specific neurotransmitter receptor sites on the receiving end of dendrites of adjacent nerve cells. Receptors are membrane proteins that recognize and bind to neurotransmitters from other cells.

When these receptors are activated, they open channels through the cell membrane into the receiving nerve cell's interior or start other processes that determine what the receiving nerve cell will do. Some neurotransmitters inhibit nerve cell function; that is, they make a neuron less likely to send electrical signals down its axon. Other neurotransmitters stimulate nerve cells; they prime the receiving cell to become active or send an electrical signal. In this way, signals travel back and forth across the neurons or connections in the brain in a fraction of a second. Millions of signals are flashing through the brain at any one time.

Groups of neurons in the brain have specific jobs. For example, some of the neurons in the brain's cerebral cortex, an outer layer of neurons all over the surface of the brain, are involved in thinking, learning, remembering, and planning.

The survival of neurons in the brain depends on the healthy functioning of several processes all working in harmony. These processes involve neuronal activities related to inter-cellular communication, cellular metabolism, and cell and tissue repair. The first process, communication between neurons, depends on the integrity of the neuron and its connections, as well as the production of neurotransmitters. The loss or absence of any one of the parts in this process disrupts cell-to-cell communication and interferes with normal brain function.

The second process is metabolism, the pathway(s) by which cells and molecules break down chemicals and nutrients to generate energy. This energy is then used to replenish the building blocks necessary for optimal neuronal function. Efficient metabolism requires adequate blood circulation to supply the cells with oxygen and important nutrients, such as glucose (a sugar). Glucose is the only source of energy available to the brain under normal circumstances. Depriving the brain of oxygen or glucose causes neurons to die within minutes.

The third process is the repair of injured neurons. Unlike most other body cells, neurons must live a long time. Brain neurons have the capacity to last more than 100 years. In an adult, when neurons die because of disease or injury, they are not usually replaced (the exceptions are neurons in particular locations and of a particular type). To prevent their own death, living neurons must constantly maintain and remodel themselves. If cell cleanup and repair slows down or stops for any reason, the nerve cell cannot function properly. It is not clear when and why some neurons start to die and some synapses stop working.

Research shows that the damage seen in Alzheimer's disease involves changes in all three of these processes: nerve cell communication, metabolism, and repair.

Many studies have centered on identifying the enzymes that cause beta-amyloid to be formed and on determining exactly how they work. By seeking clues in the beta-amyloid environment, scientists hope to understand just how beta-amyloid aggregates to form the plaques that build up in huge numbers in particular regions of the brain. Results from very recent research suggest that beta-amyloid is formed inside a part of the cell called the trans-Golgi network. Other work has found that certain organelles in the neuron, called early endosomes, are much larger in brains affected by some forms of AD than are endosomes in healthy brains, giving scientists clues about some intracellular processes affected by AD.

It is logical to expect that as the disease progresses, more and more plaques will be formed, filling more and more of the brain. However, this is not necessarily the case. In fact, the amount of beta-amyloid often seems to be relatively constant over time. Studies with a confocal scanning laser microscope, which allows investigators to view the three-dimensional structure of plaques, have revealed that plaques are not solid, but have minute holes through them. It may be that the beta-amyloid is aggregating and disaggregating at the same time, in a sort of dynamic equilibrium. This raises the hope that it may be possible to break down the plaques after they have formed.

Many scientists believe that beta-amyloid is toxic to neurons, perhaps by causing inflammation in the brain or by generating free radicals (a particular type of molecule that easily reacts with other molecules and that can be harmful if too many are produced). Another harmful effect of beta-amyloid may be that it makes neurons more susceptible to different kinds of damage, for example that caused by ischemia (poor blood flow). The neurons become more susceptible because beta-amyloid disrupts connections between cells in the immediate area around the plaque and reduces the ability of some blood vessels in the brain to dilate and compensate for the diminished blood flow. Beta-amyloid could also cause damage by increasing intracellular calcium. Calcium is an element that helps cells do many things, including carry nerve signals. However, too much calcium inside cells leads to cell death.

National Institutes of Health
National Institute on Aging

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