Alzheimer's disease is a brain disorder that currently affects around 5.3 million Americans. It can impact several areas of the brain, and damage gets progressively worse the longer a person lives with the disorder. Damage leads to not only one of the most recognized symptoms of Alzheimer's disease---memory loss---but also to problems with behavior, depression, sleep and 'cognitive' functions such as planning, attention and decision making.
Overall Damage
While everyone who ages experiences loss of brain grey matter (the part that contains the main body of cells), this is normally less than 1 percent per year. For people with Alzheimer's disease this can occur at a rate of between 3 to 9 percent per year, and some people show up to 50 percent loss by the time they die.
Neurofibrillary Tangles
In Alzheimer's disease direct damage to the main processing cells in the brain---the neurons---is through the formation of 'neurofibrillary tangles' (NFTs) composed of a protein called 'tau.' Tau is normally involved in retaining the structure of neurons, however in Alzheimer's disease strands of this protein become tangled together in pairs. This first occurs at the ends of the neurons---the dendrites and synapses---where chemical signals are passed to neighboring cells, and then progressively occurs in more of the cell, so eventually the neuron stops being able to pass and create any signals, and it may die.
Plaques
Neuritic plaques are located outside of cells and are mainly composed of materials called beta-amyloid and apolipoprotien E (ApoE). Beta-amyloid comes from a protein thought to play a role in neuronal function, and ApoE is involved in neuronal repair. The plaques themselves may not actually damage the brain, and are found in most people as they age, but they may trigger local inflammation that can harm any cells in the area.
Brain Regions Affected
The loss of grey matter in Alzheimer's disease is found first in memory-related areas of the brain known as the hippocampus and the entorhinal cortex, followed by areas that affect 'cognitive' functions---the temporal, frontal and parietal lobes---and then an area that controls movement---the midbrain. The increasing memory, then cognitive, behavioral and motor problems seen in Alzheimer's disease are a reflection of this progressive spreading of damage.
Neurotransmitters Affected
Neurons signal to each other via chemicals called neurotransmitters. The main neurotransmitter lost in Alzheimer's disease is known as acetylcholine. Many of the medications used to help slow the symptoms of Alzheimer's disease work by enhancing the levels of this neurotransmitter. Acetylcholine is involved in many aspects of memory, learning, problem solving and judgment, as well as some aspects of behavior.
Other neurotransmitters can also be affected in people with Alzheimer's disease. For example, memory problems have been linked to the loss of neurons containing glutamate. In addition, behavioral problems in people with Alzheimer's disease have been linked to loss of neurons containing dopamine, depressive symptoms to the loss of neurons containing norepinephrine and sleep problems to those containing serotonin.
References
- "Acta Neuropathologica"; Neuropathology of Alzheimer Disease: Pathognomonic But Not Pathogenic; Rudy Castellani et al; June 2006
- "Current Pharmaceutical Design"; Functional Neurochemistry of Alzheimer's Disease; Wieland Gsell et al; January 2004
- "Seminars in Neurology"; Alzheimer's Disease; Roy Yaari and Jody Corey-Bloom; February 2007
