The healthy human brain is made up of billions of different kinds of neurons that are connected through chemical and electrical signals. A typical neuron has a nucleus in a cell body, an axon, and many dendrites. Neuronal function is supported by other kinds of cells called glial cells.
As with all cells, the nucleus of a neuron contains the cell’s genetic blueprint and helps regulate the cell’s activities in response to signals from outside and inside the cell. The axon transmits messages to other neurons. Dendrites receive messages from axons of other nerve cells or from specialized sense organs. The survival of neurons depends on the healthy functioning of several interdependent processes:
- Communication. When a neuron receives enough messages from surrounding cells, an electrical charge is generated that travels to the end of the axon. Here, it triggers the release of chemicals called neurotransmitters that move across a gap, or synapse, to the dendrites of neighboring neurons. Scientists estimate that the typical neuron has up to 15,000 synapses. The neurotransmitters bind to specific receptor sites on the dendrites of neighboring neurons, triggering chemical changes and building up new electrical charges.
- Metabolism. This process encompasses all the chemical reactions that take place in the cell. Efficient metabolism requires adequate blood circulation to supply the cells with oxygen and glucose, the brain’s major fuel.
- Repair. Neurons are programmed to live a long time—even more than 100 years—so they must constantly maintain, repair, and remodel themselves.
How Does AD Affect the Brain?
In healthy aging, most types of brain neurons are not lost in large numbers. In AD, however, many neurons stop functioning, lose connections with other neurons, and die because communication, metabolism, and repair are disrupted.
At first, AD typically destroys neurons in parts of the brain that control memory, including the entorhinal cortex, the hippocampus, and related structures. AD later attacks areas responsible for language and reasoning. Eventually, many other areas of the brain are damaged, and the person becomes helpless and unresponsive to the outside world.
What are the Main Characteristics of the Brain in AD?
Many changes take place in the brain of a person with AD. The three major characteristics that reflect the pathology, or damage, caused by the disease are:
- Amyloid plaques. Found in the spaces between neurons, plaques consist of largely insoluble deposits of aggregated protein fragments called beta-amyloid peptides, other proteins, remnants of neurons, degenerating dendrites and axons, glia, and other cellular material. Scientists used to think that plaques caused the damage to neurons seen in AD. Now, however, many think that earlier, more soluble forms of beta-amyloid may be the major culprits.
- Neurofibrillary tangles. Found inside neurons, neurofibrillary tangles are abnormal aggregates of a protein called tau. Healthy neurons are internally supported in part by structures called microtubules, which help guide nutrients and molecules from the cell body to the ends of the axon. Tau, which normally has a certain number of phosphate molecules attached to it, binds to microtubules and stabilizes them. In AD, an abnormally high number of additional phosphate molecules attach to the tau. As a result, tau disengages from the microtubules and begins to clump together with other threads of tau, eventually forming neurofibrillary tangles. When this happens, the microtubules disintegrate and the neuron’s transport system collapses. As with beta-amyloid, some scientists think that early soluble forms of abnormal tau may cause the damage to neurons.
- Loss of connections between cells and cell death. This feature of AD likely results from the accumulation of beta-amyloid and abnormal tau. When neurons lose their connections, they cannot function properly and eventually die. As neuronal death spreads through the brain, affected regions begin to shrink in a process called brain atrophy. By the final stage of AD, damage is widespread, and brain tissue has shrunk significantly.
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What Causes AD?
Very rarely, people develop AD in their 30s, 40s, and 50s. In many of these cases, the disease runs in families and is caused by a mutation in one of three genes that a person has inherited from a parent. This form of the disease is called “early-onset” AD. Other early-onset cases are not caused by such mutations.
More than 90 percent of AD cases develop in people older than 60. The development and pathology of this form of AD, called “late-onset” AD, are very similar to those of early-onset AD. We don’t yet completely understand the causes of late-onset AD, but they probably include genetic, environmental, and lifestyle factors. The importance of these factors in increasing or decreasing the risk of developing AD differs from person to person. Scientists hope that what they learn about early-onset AD also can be applied to the late-onset form of the disease.
Perhaps the greatest mystery is why AD largely strikes elderly people. Why does it take 30 to 50 years for people to develop signs of the disease? Research on how the brain changes normally as people age will help provide answers to this important question.
How Is AD Diagnosed?
Clinicians use a range of tools to diagnose “possible AD” (dementia that could be due to another condition) or “probable AD” (no other cause of dementia can be found). These tools include a medical history; physical exam; tests that measure memory, language skills, and other abilities related to brain functioning; and brain scans. Knowledge about the clinical and behavioral characteristics of the disease also helps in diagnosing AD. At this time, AD can be diagnosed conclusively only by an autopsy of the brain after death. However, in specialized research facilities, clinicians can diagnose AD in a living person with up to 90 percent accuracy.
Early, accurate diagnosis is crucial because it tells people whether they have AD or whether their symptoms are being caused by something else. Stroke, tumor, Parkinson’s disease, sleep disturbances, or side effects of medications are all known to affect cognitive function and memory. Early diagnosis also helps families plan for the future while the person with AD can still participate in making decisions. Researchers are making progress in developing accurate diagnostic tests and techniques that may one day be used in general medical practice to detect the disease early—ideally before symptoms emerge.
How Is AD Treated?
A variety of treatments address behavioral and psychiatric problems that occur as AD progresses. Only a few medications have been approved by the U.S. Food and Drug Administration (FDA) to help control the cognitive loss that characterizes AD. Donepezil (Aricept®), rivastigmine (Exelon®), and galantamine (Razadyne®, formerly known as Reminyl®) are prescribed to treat mild to moderate AD symptoms. Donepezil also is approved to treat severe AD. These drugs act by stopping or slowing the action of acetylcholinesterase, an enzyme that breaks down acetylcholine (a neurotransmitter that helps in memory formation). The drugs maintain some patients’ abilities to carry out activities of daily living and may maintain some thinking, memory, or speaking skills. They also may help with certain behavioral symptoms. However, they do not stop or reverse AD and appear to help patients only for months to a few years.
Another type of AD medication, memantine (Namenda®), is prescribed to treat moderate to severe AD symptoms. This drug appears to work by regulating levels of glutamate, another neurotransmitter involved in memory function. Like the cholinesterase inhibitors, memantine does not stop or reverse AD.
In addition to these medications, physicians use other drugs and nondrug approaches to treat behavioral and psychiatric problems associated with AD. These problems include agitation, verbal and physical aggression, wandering, depression, sleep disturbances, and delusions.
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