Many changes take place in the brain of a person with Alzheimer's disease. Some of these changes can be observed in brain tissue under the microscope after death. The three abnormalities most evident in the brains of people who have died with the disorder are:
Amyloid plaques. Found in the spaces between neurons, plaques consist predominantly of abnormal deposits of a protein fragment called beta-amyloid. Beta-amyloid is formed from the breakdown of a larger protein called amyloid precursor protein (APP). Beta-amyloid comes in several different molecular forms. One of these, beta-amyloid 42, has a strong tendency to clump together. When produced in excess, beta-amyloid 42 accumulates into plaques. Scientists used to think that amyloid plaques were the primary cause of the damage to neurons seen in Alzheimer's. Now, however, many think that unclumped forms of beta-amyloid, seen earlier in the plaque formation process, may be the major culprits. Scientists have not yet determined if plaques are a cause or a byproduct of Alzheimer's disease.
Neurofibrillary tangles. Found inside neurons, neurofibrillary tangles are abnormal clumps 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 axon and dendrites. Researchers believe that tau normally binds to and stabilizes microtubules.
In Alzheimer's disease, however, tau undergoes abnormal chemical changes that cause it to detach from microtubules and stick to other tau molecules, forming threads that eventually clump together to form tangles. The tangles disrupt the microtubule network and create blocks in the neuron's transport system. Abnormal tau may also cause blocks in synaptic signaling. As with beta-amyloid, some scientists think that other, smaller forms of abnormal tau may cause the most damage to neurons.
Loss of neuronal connections and cell death. In Alzheimer's disease, the synaptic connections between certain groups of neurons stop functioning and begin to degenerate. This degeneration may be due to the abnormal deposits of beta-amyloid and tau. When neurons lose their connections, they cannot function properly and eventually die. As neuronal injury and death spread through the brain, connections between networks of neurons break down, and affected regions begin to shrink in a process called brain atrophy. By the final stage of Alzheimer's, damage is widespread, and brain tissue has shrunk significantly.