The AD Brain - Plaques and Tangles
When compared to the brains of people who are aging normally, the brains of people who have AD contain large numbers of plaques, particularly in the hippocampus, the region of the brain that controls memory. In addition, individuals with AD have a significant amount of neurofibrillary tangles spread throughout the brain.
Interestingly, doctors have found some people who showed no symptoms of Alzheimer's Disease and still had a significant number of plaques and tangles in their brains at autopsy. These people may have developed a so called "cognitive reserve," or a large number of connections between brain cells due to healthy lifestyle habits (discussed later) and a high level of education which acted like a "buffer" to stave off the symptoms of the disease. Another theory is that plaques and tangles begin to form several years before Alzheimer's symptoms actually appear, so people who have plaques and tangles but no signs of AD may have died of another cause before living long enough to become cognitively impaired.
Because of this mystery (why some people with large amounts of plaques and tangles don't have AD symptoms), many scientists believe there is more to Alzheimer's Disease than abnormal protein accumulations, although these do seem to play a significant role in the development of the disease.
The AD Brain - Free Radicals
Individuals with Alzheimer's Disease seem to have double the amount of destruction created by free radicals in the frontal and temporal (side) portions of the brain when compared to people aging normally. Both of these brain areas are important for memory and other advanced cognitive functions.
The AD Brain - Neurotransmitters
Neurotransmitters are chemicals that carry messages between neurons so that the cells can function properly. If the brain produces too much or too little of a particular neurotransmitter, problems such as memory impairment, confusion, or depression can occur. While most scientists do not think that changes in neurotransmitter levels cause AD, neurotransmitter levels are affected by the illness and contribute to the thinking problems that accompany it. Several medications used to treat symptoms of Alzheimer's Disease target neurotransmitters, which provides indirect evidence that these brain chemicals are somehow involved.
Two neurotransmitters seem to play a role in Alzheimer's Disease: acetylcholine and glutamate. Acetylcholine (ACh) activates muscles and helps with arousal, short-term memory, and learning. Individuals with AD have low levels of ACh. Some research suggests that plaques may be one of the reasons for low levels of ACh because they increase the activity of a chemical called acetylcholinesterase, which is involved in breaking down ACh. Too much acetylcholinesterase has the overall effect of decreasing ACh levels, which contributes to the characteristic symptoms of AD.
Glutamate is the most common neurotransmitter in the brain and is involved in learning and memory. As the brain cells of someone with Alzheimer's Disease die, they release excess amounts of glutamate. The excess glutamate becomes harmful because it overstimulates healthy brain cells (a phenomenon called excitotoxicity), causing them to become damaged or to die.
The AD Brain - The Path of Destruction
AD starts in a part of the brain called the entorhinal cortex (EC), which sends signals to the hippocampus that help form and store memories. Plaques and tangles then spread to the hippocampus and other parts of the brain that control memory, language, and reasoning. As brain regions are destroyed, they atrophy or shrink. As a result, the fluid-filled chambers of the brain (called ventricles) enlarge, and sulci (tissue indentations) widen. Eventually, large portions of the brain are completely destroyed by AD.