Alzheimer's Disease : Plaques and Tangles, Changing Brain

by National Institute on Aging

(Page 4 of 16)

Alzheimer's disease disrupts each of the three processes that keep neurons healthy: communication, metabolism, and repair. This disruption causes certain nerve cells in the brain to stop working, lose connections with other nerve cells, and finally, die. The destruction and death of nerve cells causes the memory failure, personality changes, problems in carrying out daily activities, and other features of the disease.

The brains of AD patients have an abundance of two abnormal structures - beta amyloid plaques and neurofibrillary tangles. This is especially true in certain regions of the brain that are important in memory. Plaques are dense, mostly insoluble (cannot be dissolved) deposits of protein and cellular material outside and around the neurons. Tangles are insoluble twisted fibers that build up inside the nerve cell. Though many older people develop some plaques and tangles, the brains of AD patients have them to a much greater extent. Scientists have known about plaques and tangles for many years, but recent research has shown much about what they are made of, how they form, and their possible roles in AD.

Plaques and Tangles: The Hallmarks of AD

Alzheimer's disease disrupts each of the three processes that keep neurons healthy: communication, metabolism, and repair. This disruption causes certain nerve cells in the brain to stop working, lose connections with other nerve cells, and finally, die. The destruction and death of nerve cells causes the memory failure, personality changes, problems in carrying out daily activities, and other features of the disease.

The brains of AD patients have an abundance of two abnormal structures - beta amyloid plaques and neurofibrillary tangles. This is especially true in certain regions of the brain that are important in memory. Plaques are dense, mostly insoluble (cannot be dissolved) deposits of protein and cellular material outside and around the neurons. Tangles are insoluble twisted fibers that build up inside the nerve cell. Though many older people develop some plaques and tangles, the brains of AD patients have them to a much greater extent. Scientists have known about plaques and tangles for many years, but recent research has shown much about what they are made of, how they form, and their possible roles in AD.

Neurofibrillary Tangles

Healthy neurons have an internal support structure partly made up of structures called microtubules. These microtubules act like tracks, guiding nutrients and molecules from the body of the cell down to the ends of the axon and back. A special kind of protein, tau, makes the microtubules stable. In AD, tau is changed chemically. It begins to pair with other threads of tau and they become tangled up together. When this happens, the microtubules disintegrate, collapsing the neuron's transport system. This may result first in malfunctions in communication between neurons and later in the death of the cells.

The Changing Brain in Alzheimer's Disease

No one knows exactly what causes the Alzheimer's disease process to begin or why some of the normal changes associated with aging become so much more extreme and destructive in patients with the disease. We do know a lot, however, about what happens in the brain once AD takes hold and about the physical and mental changes that occur over time. The time from diagnosis to death varies - as little as 3 years if the patient is over 80 when diagnosed, as long as 10 or more years if the patient is younger. Although the course of AD is not the same in every patient, symptoms seem to develop over the same general stages.

Preclinical AD

AD begins in the entorhinal cortex, which is near the hippocampus and has direct connections to it. It then proceeds to the hippocampus, the structure that is essential to the formation of short-term and long-term memories. Affected regions begin to atrophy (shrink). These brain changes probably start 10 to 20 years before any visible signs and symptoms appear. Memory loss, the first visible sign, is the main feature of mild cognitive impairment (MCI). Many scientists think MCI is often an initial, transitional phase between normal brain aging and AD.

Mild AD

As the disease begins to affect the cerebral cortex, memory loss continues and changes in other cognitive abilities emerge. The clinical diagnosis of AD is usually made during this stage. Signs of mild AD can include:

• Memory loss
• Confusion about the location of familiar places (getting lost begins to occur)
• Taking longer to accomplish normal daily tasks
• Trouble handling money and paying bills
• Poor judgment leading to bad decisions
• Loss of spontaneity and sense of initiative
• Mood and personality changes, increased anxiety

About the Author

www.nia.nih.gov
NIA, one of the 27 Institutes and Centers of NIH, leads a broad scientific effort to understand the nature of aging and to extend the healthy, active years of life. In 1974, Congress granted authority to form NIA to provide leadership in aging research, training, health information dissemination, and other programs relevant to aging and older people.