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What Are the Main Characteristics of AD?:Neurofibrillary Tangles

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By 1999 Progress Report by the NIA/NIH • www.ProHealth.com • December 13, 1999


This second hallmark of AD consists of abnormal collections of twisted threads found inside nerve cells. The chief component of tangles is one form of a protein called tau. In the central nervous system, tau proteins are best known for their ability to bind and help stabilize microtubules, which are one constituent of the cell's internal support structure, or skeleton.

In healthy neurons, microtubules form structures like train tracks, which guide nutrients and molecules from the bodies of the cells down to the ends of the axon, a long thin structure that extends far out from the cell body and forms a communicating bridge with other neurons. In cells affected by AD, the train track structures collapse. Tau normally forms the "railroad ties" or connector pieces of the microtubule tracks. However, in AD tau is changed chemically, and this altered tau can no longer hold the railroad tracks together, causing the microtubules to fall apart. This collapse of the transport system first may result in malfunctions in communication between nerve cells and later may lead to neuronal death.

New Research Shatters a Longstanding Belief about Neurons

Until now, scientists always thought that neurons were formed only during the fetal period and for a short time after birth. Once a person had his or her full complement of neurons, that was that--the adult human body could not create new ones.

This past year, that idea changed dramatically as a result of research supported in part by NIA. Building on work in rodents, researchers at the Institute of Neurology, Sahlgrenska University Hospital, Goteborg, Sweden, and at the Salk Institute in La Jolla, California, discovered that the human brain does indeed retain an ability to generate neurons throughout life (Eriksson et al., 1998). In this study, cancer patients received injections of a compound called BrdU, which was used for diagnostic purposes. The BrdU was incorporated into the cells' DNA as they divided. Upon examining brain tissue from the patients after their death, the investigators found BrdU-labeled neurons and glial cells in the hippocampal region. This meant that these adult human brains contained dividing neuronal stem cells (the specialized cells that generate neurons and glial cells).

Although more research will be necessary to understand the biological significance of these findings, they are provocative and may have an enormous impact on future aging research. By demonstrating that new neurons can be generated in the adult brain, it may now be possible to stimulate intrinsic brain repair mechanisms to replace neurons and glial cells lost through age, trauma, and disease. Alzheimer's and Parkinson's diseases, strokes, and spinal cord injuries are all characterized by neuronal dysfunction and death. Finding ways to stimulate the formation of new brain and spinal cord neurons may one day lead to novel therapeutic approaches for these and other conditions.

In AD, chemically altered tau twists into paired helical filaments--two threads of tau that are wound around each other. These filaments are the major substance found in neurofibrillary tangles. In one recent study, researchers found neurofibrillary changes in fewer than 6 percent of the neurons in a particular part of the hippocampus in healthy brains, in more than 43 percent of these neurons in people who died with mild AD, and in 71 percent of these neurons in people who died with severe AD. When they studied the loss of neurons, they found a similar progression. Evidence of this type supports the idea that the formation of tangles and the loss of neurons progress together over the course of AD.

Source:
National Institutes of Health
National Institute on Aging
1999 PROGRESS REPORT ON ALZHEIMER'S DISEASE



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