The Pathology of Alzheimer’s Disease

Neurofibrillary tangles are abnormal accumulations of the protein tau that collects inside neurons. Healthy neurons, in part, are supported internally by structures called microtubules. In healthy neurons, tau normally binds to and stabilizes microtubules. In Alzheimer’s disease, however, abnormal chemical changes cause tau to detach from microtubules and stick to other tau molecules, forming threads that eventually join to form tangles inside neurons. These tangles block the neuron’s transport system, harming the synaptic communication between neurons.

Emerging evidence suggests that Alzheimer’s-related brain changes may result from a complex interplay among abnormal tau and amyloid plaque proteins and several other factors. It appears that abnormal tau accumulates in specific brain regions involved in memory. Amyloid clumps into plaques between neurons. As the level of amyloid plaques reaches a tipping point, there is a rapid spread of tau throughout the brain.

Research suggests that chronic inflammation may be caused by the buildup of glial cells normally meant to help keep the brain free of debris. One type of glial cell, microglia, engulfs and destroys waste and toxins in a healthy brain. In Alzheimer’s, microglia fail to clear away waste, debris, and protein collections, including amyloid plaques.