Ironically, the nerve cells in brain circuits that serve learning and memory and higher cognitive functions are the most vulnerable to Alzheimer's disease. Many believe that those cells that are the most sensitive and sophisticated for encoding change also are the most vulnerable. The final pathological signatures in the Alzheimer's-diseased brain are synaptic loss, neuronal death, and the formation of neuronal tangles and senile plaques. Over the last several years, much new and exciting research has led to a better understanding of the reasons that these changes occur. The signature of tangles and plaques in the Alzheimer's disease brain was first observed by Alois Alzheimer in 1907.
Tangles are abnormal collections of neurons that contain twisted threads.
The chief component of tangles is a form of a protein called tau that is involved in the trafficking of molecules in and out of the cell body. In cells affected by Alzheimer's disease, tau functions collapse and intracellular trafficking becomes progressively disrupted, leading to a breakdown in communication between nerve cells and, ultimately, to nerve cell death. A new mechanism to account for neuronal death, particularly in early-stage cases, is apoptosis. Plaques are deposits of a protein called beta-amyloid, along with fragments of dead, dying neurons and other molecules that accumulate over time as a dense, insoluble structure in the brain. Amyloid also appears to be toxic to nerve cells and their processes and appears to drive inflammatory responses, or immune responses, that can contribute to oxidative damage.