During the past few decades, a great deal has been learned about the changes that occur in the brain of individuals who have late-onset Alzheimer's disease. While a diagnosis of Alzheimer's disease is often suspected while an individual is alive, the diagnosis can only be confirmed through careful examination of the brain after death.
The lack of communication between nerve cells (neurons) is the fundamental cause for the memory loss that is so characteristic of Alzheimer's disease. The two main pathologic abnormalities observed in the brain of patients with Alzheimer's disease are the senile (neuritic) plaques (see figure A) and the neurofibrillary tangles (see figure B). These abnormalities can only be seen with the aid of a microscope.
Senile plaque and Neurofibrillary tangle
The core of the amyloid plaques contains a large amount of a protein called beta amyloid. The plaques are located in the space between the cell bodies of neurons. Typically, plaques are located in a part of the brain called the hippocampus, where memories are encoded, and in other regions of the cerebral cortex that are important for thinking and making decisions. The amyloid plaques are dense and do not dissolve. As an individual's disease worsens, the number of plaques increases and their distribution in the brain will often spread.
In contrast to amyloid plaques, which are located outside the neurons, neurofibrillary tangles are found inside the brain cells. In healthy cells, microtubules are involved in the transport of material inside cells. Tau is a protein that works with microtubules in this transport system. In Alzheimer's disease, tau is severely altered and begins to clump together to form tangles. As a consequence, there is an impairment of the transport system that eventually contributes to the death of the cell.
The presence of amyloid plaques and neurofibrillary tangles may be found in individuals who did not have any detectable clinical symptoms of Alzheimer's disease during their lifetime. Therefore, it is critical to document the number of amyloid plaques and neurofibrillary tangles and where they are located in the brain. Neuropathologists have established several classification systems whereby they can grade the severity of the amyloid plaques and neurofibrillary tangles.